CN100457747C - Preparation process of key intermediate 5-cyanphthalide of antidepressant drug citalopram - Google Patents
Preparation process of key intermediate 5-cyanphthalide of antidepressant drug citalopram Download PDFInfo
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- CN100457747C CN100457747C CNB2006101547213A CN200610154721A CN100457747C CN 100457747 C CN100457747 C CN 100457747C CN B2006101547213 A CNB2006101547213 A CN B2006101547213A CN 200610154721 A CN200610154721 A CN 200610154721A CN 100457747 C CN100457747 C CN 100457747C
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- Prior art keywords
- cyanophthalide
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- key intermediate
- cuprous iodide
- antidepressant drug
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- XEEGWTLAFIZLSF-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carbonitrile Chemical compound N#CC1=CC=C2C(=O)OCC2=C1 XEEGWTLAFIZLSF-UHFFFAOYSA-N 0.000 title claims description 25
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 title claims description 12
- 229960001653 citalopram Drugs 0.000 title claims description 12
- 239000000935 antidepressant agent Substances 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 11
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims abstract description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims abstract description 21
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims abstract description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 11
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000004996 alkyl benzenes Chemical class 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- IUSPXLCLQIZFHL-UHFFFAOYSA-N 5-bromo-3h-2-benzofuran-1-one Chemical compound BrC1=CC=C2C(=O)OCC2=C1 IUSPXLCLQIZFHL-UHFFFAOYSA-N 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 235000007715 potassium iodide Nutrition 0.000 claims description 14
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 12
- 229960004839 potassium iodide Drugs 0.000 claims description 11
- 238000005516 engineering process Methods 0.000 claims description 10
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 8
- 230000006837 decompression Effects 0.000 claims description 8
- 235000019441 ethanol Nutrition 0.000 claims description 8
- 238000011084 recovery Methods 0.000 claims description 8
- 238000001953 recrystallisation Methods 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims description 5
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 3
- 239000002131 composite material Substances 0.000 abstract 1
- 239000000706 filtrate Substances 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 125000005633 phthalidyl group Chemical group 0.000 abstract 1
- 239000000047 product Substances 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 10
- 239000013078 crystal Substances 0.000 description 5
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical class [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- QTWUWCFGWYYRRL-UHFFFAOYSA-N 1-oxo-3h-2-benzofuran-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2C(=O)OCC2=C1 QTWUWCFGWYYRRL-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- FRHBUJIXNLOLOF-UHFFFAOYSA-N 3-oxo-1h-2-benzofuran-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)OC(=O)C2=C1 FRHBUJIXNLOLOF-UHFFFAOYSA-N 0.000 description 1
- YBKVTRRHIGZPGV-UHFFFAOYSA-N N#CC1=CC=C2C(=O)OCC2=C1.N#CC1=CC=C2C(=O)OCC2=C1 Chemical compound N#CC1=CC=C2C(=O)OCC2=C1.N#CC1=CC=C2C(=O)OCC2=C1 YBKVTRRHIGZPGV-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- WXIUBYCJAAEOFL-UHFFFAOYSA-N [S].ClOCl Chemical compound [S].ClOCl WXIUBYCJAAEOFL-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- -1 organic acid ammonium salt Chemical class 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a prapring method of key intermediate of 5-cyanobenzene phthalidyl to prevent depression, which comprises the following steps: adopting alkyl benzene as reacting solvent; making 1.5-3% cuprous iodide, potassium iodide and 1-1.5% N, N'-dimethyldiamine as composite catalyst; reacting 5-brobenzene phthalidyl and sodium cyanide with molar rate at 1: 1.0-2.0 protected by nitrogen at 100-150 Deg C for 20-48h; filtering; decompressing the filtrate; fractioning to obtain the product. The invention shortens reacting flow path, which is simple to feed and dispose.
Description
Technical field
The present invention relates to the medicine intermediate preparation method, relate in particular to a kind of preparation technology of antidepressant drug citalopram key intermediate 5-cyanophthalide.
Background technology
The chemistry of 5-cyanophthalide (5-Cyano-phthalide) is called 1, and 3-dihydro-1-oxygen-5-isobenzofuran nitrile is the key intermediate of synthetic antidepressant drug citalopram (Citalopram).Therefore how to synthesize the huge concern that the 5-cyanophthalide is subjected to people efficiently.Synthetic more existing bibliographical informations of 5-cyanophthalide, such as document WO 00 112 044,2000-03-09 report is that starting raw material makes 5 one carboxyl phthalides under the oleum effect with phthalic acid and Paraformaldehyde 96, makes through reaction such as sulfur oxychloride chloride, ammoniacal liquor amidation and tetramethylene sulfone dehydration.Document " chemistry and biotechnology " 2006, Vol.23, No.6,17-18 and " Chinese Journal of Pharmaceuticals " 2004,35 (6), 330-331 etc. are starting raw material with the phthalic imidine through nitrated, reduction, cyclization, Sandmeyer cyanogenation, have synthesized the 5-cyanophthalide.Document CN1379025 report is a starting raw material with 5-carboxyl phthalide, obtain corresponding 5-phthalide formic acid ammonium salt with inorganic ammonia or inorganic ammonium salt or small molecular weight organic acid ammonium salt reactant salt, 5-phthalide formic acid ammonium salt, under the condition of solvent and catalyzer existence, make the 5-cyanophthalide through the dewatering agent dehydration reaction.Document CN1331686 report is converted into corresponding amide with 5-carboxyl 2-benzo [c] furanone, with the dewatering agent reaction, obtains the 5-cyanophthalide then.Above-mentioned these synthesis technique reaction process are long cycle time, the condition harshness, or have many experimentations to relate to variety of problems such as strong acid or highly basic condition, low-yield, aftertreatment complexity.Thereby under the condition of gentleness, it is very important and urgent solving the synthetic of 5-cyanophthalide efficiently.
Summary of the invention
The preparation technology who the purpose of this invention is to provide a kind of antidepressant drug citalopram key intermediate 5-cyanophthalide.
It is to be reaction solvent with the alkylbenzene, with cuprous iodide, potassiumiodide and N, N '-dimethyl-ethylenediamine is a combination catalyst, 100～150 ℃ of reactions 20～48 hours, decompression and solvent recovery then added entry subsequently under nitrogen protection for 5-bromo phthalide and sodium cyanide, filter, washing leaches thing at last and obtains the 5-cyanophthalide with the ethyl alcohol recrystallization separation, and the molar equivalent ratio of 5-bromo phthalide and sodium cyanide is 1: 1.0～2.0; The consumption of cuprous iodide is 5～30% molar equivalents of 5-bromo phthalide, and the consumption of potassiumiodide is 1.5～3 molar equivalents of cuprous iodide; N, the consumption of N '-dimethyl-ethylenediamine are 1～1.5 molar equivalent of 5-bromo phthalide, and reaction formula is:
Described reaction solvent alkylbenzene is toluene, ethylbenzene or dimethylbenzene.Reaction times is preferably 20～36 hours.Temperature of reaction is preferably 100～130 ℃.The molar equivalent ratio of 5-bromo phthalide and sodium cyanide is preferably 1: 1.0～and 1.5; The consumption of cuprous iodide is 5～20% molar equivalents of 5-bromo phthalide; The consumption of potassiumiodide is preferably 1.5～2.5 molar equivalents of cuprous iodide; N, the consumption of N '-dimethyl-ethylenediamine are preferably 1～1.2 molar equivalent of 5-bromo phthalide.
The present invention compares with existing synthetic method, has the following advantages:
1) reaction conditions gentleness;
2) the reaction process flow process is short;
3) use cheap reagent;
4) feed intake and aftertreatment all very simple, be easy to realize industrialized production.
Embodiment
The molecular formula of 5-cyanophthalide is:
The preparation technology's of antidepressant drug citalopram key intermediate 5-cyanophthalide concrete reactions steps is as follows:
With the alkylbenzene is reaction solvent; with cuprous iodide, potassiumiodide and N; N '-dimethyl-ethylenediamine is a combination catalyst; 5-bromo phthalide and sodium cyanide reacted 20～48 hours at 100～150 ℃ under nitrogen protection; decompression and solvent recovery then adds entry subsequently, filters; washing leaches thing at last and obtains high yield, highly purified 5-cyanophthalide with the ethyl alcohol recrystallization separation.Wherein the molar equivalent ratio of 5-bromo phthalide and sodium cyanide is 1: 1.0～2.0; The consumption of cuprous iodide is 5～30% molar equivalents of 5-bromo phthalide; The consumption of potassiumiodide is 1.5～3 molar equivalents of cuprous iodide; N, the consumption of N '-dimethyl-ethylenediamine are the 1-1.5 molar equivalent of 5-bromo phthalide.Recommendation response solvent alkylbenzene is toluene, ethylbenzene, dimethylbenzene, and override is a toluene.The recommendation response time is 20～36 hours, and override is 24 hours.The recommendation response temperature is 100～130 ℃, and override is 110 ℃.Recommending the molar equivalent ratio of 5-bromo phthalide and sodium cyanide is 1: 1.0～1.5, and override is 1: 1.2; The consumption of cuprous iodide is 5～20% molar equivalents of 5-bromo phthalide, and override is 10% molar equivalent; The consumption of potassiumiodide is 1.5～2.5 molar equivalents of cuprous iodide, and override is 2 molar equivalents; N, N '-dimethyl-ethylenediamine consumption are 1～1.2 molar equivalent of 5-bromo phthalide, and override is 1 molar equivalent.Following examples will help to understand the present invention, but be not limited to content of the present invention:
Embodiment 1
In 100 milliliters of three-necked bottles; add 50 milliliters of toluene under the nitrogen protection successively; 6.4 gram (30 mmole) 5-bromo phthalide, 1.18 gram (36 mmoles, 1.2 equivalents) sodium cyanides; 0.573 gram (3 mmoles; 0.1 cuprous iodide equivalent), 1 gram potassiumiodide (6 mmoles, 0.2 equivalent); 2.64 gram N; N '-dimethyl-ethylenediamine (30 mmoles, 1.0 equivalents), under nitrogen protection 110 ℃ of stirring reactions 30 hours; finish reaction; decompression and solvent recovery toluene, residue then add 50 ml waters, stirring at room 1 hour; filter; washing leaches thing at last and obtains white needle-like crystals 5-cyanophthalide, productive rate 90% with the ethyl alcohol recrystallization separation; purity 98% (HPLC), 200～202 ℃ of fusing points.
1HNMR(CDCl
3，ppm)：5.51(2H，s)，7.55(1H，s)，7.55(1H，s)，8.05(1H，d，J＝2.5Hz).
Embodiment 2
In 100 milliliters of three-necked bottles; add 60 milliliters of ethylbenzene under the nitrogen protection successively; 6.4 gram (30 mmole) 5-bromo phthalide, 1.6 gram (39 mmoles, 1.3 equivalents) sodium cyanides; 0.573 gram (3 mmoles; 0.1 cuprous iodide equivalent), 1 gram potassiumiodide (6 mmoles, 0.2 equivalent); 2.64 gram N; N '-dimethyl-ethylenediamine (30 mmoles, 1.0 equivalents), under nitrogen protection 130 ℃ of stirring reactions 24 hours; finish reaction; decompression and solvent recovery ethylbenzene, residue then add 50 ml waters, stirring at room 1 hour; filter; washing leaches thing at last and obtains white needle-like crystals 5-cyanophthalide, productive rate 85% with the ethyl alcohol recrystallization separation; purity 99%, 201～202 ℃ of fusing points.
Embodiment 3
In 100 milliliters of three-necked bottles; add 50 milliliters of toluene under the nitrogen protection successively; 6.4 gram (30 mmole) 5-bromo phthalide, 1.18 gram (36 mmoles, 1.2 equivalents) sodium cyanides; 0.7 gram (4.5 mmoles; 0.15 cuprous iodide equivalent), 1.5 gram potassiumiodides (9 mmoles, 0.3 equivalent); 2.64 gram N; N '-dimethyl-ethylenediamine (30 mmoles, 1.0 equivalents), under nitrogen protection 100 ℃ of stirring reactions 48 hours; finish reaction; decompression and solvent recovery toluene, residue then add 50 ml waters, stirring at room 1 hour; filter; washing leaches thing at last and obtains white needle-like crystals 5-cyanophthalide, productive rate 91% with the ethyl alcohol recrystallization separation; purity 98%, 200～202 ℃ of fusing points.
Embodiment 4
In 100 milliliters of three-necked bottles; add 60 milliliters of dimethylbenzene under the nitrogen protection successively; 6.4 gram (30 mmole) 5-bromo phthalide, 2.5 gram (60 mmoles, 2 equivalents) sodium cyanides; 1.7 gram (9 mmoles; 0.3 cuprous iodide equivalent), 2 gram potassiumiodides (12 mmoles, 0.4 equivalent); 3.6 gram N; N '-dimethyl-ethylenediamine (45 mmoles, 1.5 equivalents), under nitrogen protection 150 ℃ of stirring reactions 20 hours; finish reaction; decompression and solvent recovery ethylbenzene, residue then add 50 ml waters, stirring at room 1 hour; filter; washing leaches thing at last and obtains white needle-like crystals 5-cyanophthalide, productive rate 83% with the ethyl alcohol recrystallization separation; purity 99%, 201～202 ℃ of fusing points.
Embodiment 5
In 100 milliliters of three-necked bottles; add 50 milliliters of toluene under the nitrogen protection successively; 6.4 gram (30 mmole) 5-bromo phthalide, 1.0 gram (30 mmoles, 1.0 equivalents) sodium cyanides; 0.7 gram (4.5 mmoles; 0.15 cuprous iodide equivalent), 1.5 gram potassiumiodides (9 mmoles, 0.3 equivalent); 2.64 gram N; N '-dimethyl-ethylenediamine (30 mmoles, 1.0 equivalents), under nitrogen protection 105 ℃ of stirring reactions 48 hours; finish reaction; decompression and solvent recovery toluene, residue then add 50 ml waters, stirring at room 1 hour; filter; washing leaches thing at last and obtains white needle-like crystals 5-cyanophthalide, productive rate 86% with the ethyl alcohol recrystallization separation; purity 98%, 200～202 ℃ of fusing points.
Claims (5)
1. the preparation technology of an antidepressant drug citalopram key intermediate 5-cyanophthalide, it is characterized in that it is is reaction solvent with the alkylbenzene, with cuprous iodide, potassiumiodide and N, N '-dimethyl-ethylenediamine is a combination catalyst, 5-bromo phthalide and sodium cyanide reacted 20～48 hours at 100～150 ℃ under nitrogen protection, decompression and solvent recovery subsequently, then add entry, filter, washing, leach thing at last and obtain the 5-cyanophthalide with the ethyl alcohol recrystallization separation, the molar equivalent ratio of 5-bromo phthalide and sodium cyanide is 1: 1.0～2.0; The consumption of cuprous iodide is 5～30% molar equivalents of 5-bromo phthalide, and the consumption of potassiumiodide is 1.5～3 molar equivalents of cuprous iodide; N, the consumption of N '-dimethyl-ethylenediamine are 1～1.5 molar equivalent of 5-bromo phthalide, and reaction formula is:
2. the preparation technology of a kind of antidepressant drug citalopram key intermediate 5-cyanophthalide according to claim 1 is characterized in that described reaction solvent alkylbenzene is toluene, ethylbenzene or dimethylbenzene.
3. the preparation technology of a kind of antidepressant drug citalopram key intermediate 5-cyanophthalide according to claim 1 is characterized in that the described reaction times is 20～36 hours.
4. the preparation technology of a kind of antidepressant drug citalopram key intermediate 5-cyanophthalide according to claim 1 is characterized in that described temperature of reaction is 100～130 ℃.
5. the preparation technology of a kind of antidepressant drug citalopram key intermediate 5-cyanophthalide according to claim 1, the molar equivalent ratio that it is characterized in that described 5-bromo phthalide and sodium cyanide is 1: 1.0～1.5; The consumption of cuprous iodide is 5～20% molar equivalents of 5-bromo phthalide; The consumption of potassiumiodide is 1.5～2.5 molar equivalents of cuprous iodide; N, the consumption of N '-dimethyl-ethylenediamine are 1～1.2 molar equivalent of 5-bromo phthalide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101547213A CN100457747C (en) | 2006-11-21 | 2006-11-21 | Preparation process of key intermediate 5-cyanphthalide of antidepressant drug citalopram |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101547213A CN100457747C (en) | 2006-11-21 | 2006-11-21 | Preparation process of key intermediate 5-cyanphthalide of antidepressant drug citalopram |
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| Publication Number | Publication Date |
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| CN1962651A CN1962651A (en) | 2007-05-16 |
| CN100457747C true CN100457747C (en) | 2009-02-04 |
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| CNB2006101547213A Expired - Fee Related CN100457747C (en) | 2006-11-21 | 2006-11-21 | Preparation process of key intermediate 5-cyanphthalide of antidepressant drug citalopram |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4136193A (en) * | 1976-01-14 | 1979-01-23 | Kefalas A/S | Anti-depressive substituted 1-dimethylaminopropyl-1-phenyl phthalans |
| CN1379025A (en) * | 2002-04-15 | 2002-11-13 | 杭州达康化工有限公司 | Process for preparing 5-cynophenyl phthaleine |
| CN1391566A (en) * | 1999-12-30 | 2003-01-15 | H.隆德贝克有限公司 | Preparation of citalopram |
-
2006
- 2006-11-21 CN CNB2006101547213A patent/CN100457747C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4136193A (en) * | 1976-01-14 | 1979-01-23 | Kefalas A/S | Anti-depressive substituted 1-dimethylaminopropyl-1-phenyl phthalans |
| CN1391566A (en) * | 1999-12-30 | 2003-01-15 | H.隆德贝克有限公司 | Preparation of citalopram |
| CN1379025A (en) * | 2002-04-15 | 2002-11-13 | 杭州达康化工有限公司 | Process for preparing 5-cynophenyl phthaleine |
Non-Patent Citations (4)
| Title |
|---|
| 5-氰基异苯并呋喃-1-酮的合成. 刘丹，孟艳秋.中国医药工业杂志,，第35卷第6期. 2004 |
| 5-氰基异苯并呋喃-1-酮的合成. 刘丹，孟艳秋. 中国医药工业杂志，第35卷第6期. 2004 * |
| 氢溴酸西酞普兰的合成. 吴秋业等.中国医药工业杂志,，第36,卷第1期. 2005 |
| 氢溴酸西酞普兰的合成. 吴秋业等. 中国医药工业杂志，第36卷第1期. 2005 * |
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