CN113061086A - Preparation method of long-chain aliphatic dicarboxylic acid mono-tert-butyl ester - Google Patents
Preparation method of long-chain aliphatic dicarboxylic acid mono-tert-butyl ester Download PDFInfo
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- CN113061086A CN113061086A CN202010001797.2A CN202010001797A CN113061086A CN 113061086 A CN113061086 A CN 113061086A CN 202010001797 A CN202010001797 A CN 202010001797A CN 113061086 A CN113061086 A CN 113061086A
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- 238000002360 preparation method Methods 0.000 title claims description 21
- 125000001931 aliphatic group Chemical group 0.000 title abstract description 12
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 title abstract description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 title abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 25
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 14
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 239000007810 chemical reaction solvent Substances 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 claims description 4
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical group [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 2
- 229910001863 barium hydroxide Inorganic materials 0.000 claims description 2
- ZUDYPQRUOYEARG-UHFFFAOYSA-L barium(2+);dihydroxide;octahydrate Chemical group O.O.O.O.O.O.O.O.[OH-].[OH-].[Ba+2] ZUDYPQRUOYEARG-UHFFFAOYSA-L 0.000 claims description 2
- DRGAZIDRYFYHIJ-UHFFFAOYSA-N 2,2':6',2''-terpyridine Chemical compound N1=CC=CC=C1C1=CC=CC(C=2N=CC=CC=2)=N1 DRGAZIDRYFYHIJ-UHFFFAOYSA-N 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 9
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 abstract description 2
- 238000012805 post-processing Methods 0.000 abstract 1
- 238000001914 filtration Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- BNJOQKFENDDGSC-UHFFFAOYSA-N octadecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCCCC(O)=O BNJOQKFENDDGSC-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- WDUQJXKBWRNMKI-UHFFFAOYSA-N 18-[(2-methylpropan-2-yl)oxy]-18-oxooctadecanoic acid Chemical compound CC(C)(C)OC(=O)CCCCCCCCCCCCCCCCC(O)=O WDUQJXKBWRNMKI-UHFFFAOYSA-N 0.000 description 2
- VLBWHFOIXBCMJQ-UHFFFAOYSA-N CC(C)(C)OC(=O)CCCCCCCCCCCCCCCCC(=O)OC(C)(C)C Chemical compound CC(C)(C)OC(=O)CCCCCCCCCCCCCCCCC(=O)OC(C)(C)C VLBWHFOIXBCMJQ-UHFFFAOYSA-N 0.000 description 2
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 2
- 102100040918 Pro-glucagon Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- QQLXPUHVMNANLN-UHFFFAOYSA-N tert-butyl 10-bromodecanoate Chemical compound CC(C)(C)OC(=O)CCCCCCCCCBr QQLXPUHVMNANLN-UHFFFAOYSA-N 0.000 description 2
- PGVRSPIEZYGOAD-UHFFFAOYSA-N 10-bromodecanoic acid Chemical compound OC(=O)CCCCCCCCCBr PGVRSPIEZYGOAD-UHFFFAOYSA-N 0.000 description 1
- XEGRKZRPTBNSMN-UHFFFAOYSA-N 9-bromononanoic acid Chemical compound OC(=O)CCCCCCCCBr XEGRKZRPTBNSMN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- -1 di-tert-butyl didecanedioate Chemical compound 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/353—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明通过对单水解的反应条件进行控制，提供了一种通过长链脂肪二羧酸二叔丁酯进行单水解得到长链脂肪二羧酸单叔丁酯的方法，原料成本低，收率较高，后处理方法简单，适合工业化生产。The present invention provides a method for obtaining long-chain aliphatic dicarboxylic acid mono-tert-butyl ester by mono-hydrolysis of long-chain aliphatic dicarboxylic acid di-tert-butyl ester by controlling the reaction conditions of monohydrolysis, with low cost of raw materials and high yield. Higher, the post-processing method is simple, suitable for industrial production.
Description
Technical Field
The invention relates to the field of pharmaceutical chemistry synthesis, and in particular relates to a preparation method of long-chain aliphatic dicarboxylic acid mono-tert-butyl ester.
Background
The glucagon-like peptide-1 (GLP-1) agonist serving as a novel hypoglycemic agent can effectively control blood sugar, obviously reduce the incidence rate of hypoglycemic events, and also has the advantages of obviously reducing weight and reducing the risk of cardiovascular events. However, natural GLP-1 is easily degraded in vivo, resulting in a short half-life, so chemical modification of GLP-1 to obtain a long-acting GLP-1 agonist has been a problem that the industry has been trying to solve.
International patent publication WO2006097537a2 discloses a class of chemically modified GLP-1 analogues with a longer half-life which are partially acylated at the lysine residue in position 26 and which comprise a long chain acidic group at the end, such as:
wherein I is 12, 13, 14. 15, 16, 17, 18, 19 or 20, which long chain acidic groups can be made from the corresponding long chain aliphatic dicarboxylic acid mono-tert-butyl ester intermediate.
The existing synthesis of long-chain aliphatic dicarboxylic acid mono-tert-butyl ester usually adopts corresponding long-chain aliphatic dicarboxylic acid to perform mono-esterification, but because the carbon chain is too long and the mono-esterification lacks selectivity, the yield is only 20-40% (WO2005082404A, WO2004035624A and CN105001140B), and the synthesis is only on gram-scale and can not meet the requirement of industrial production.
Disclosure of Invention
In order to solve the problem of low yield of long-chain aliphatic mono-tert-butyl ester, the invention provides a method for obtaining long-chain aliphatic dicarboxylic acid mono-tert-butyl ester (a compound shown in a formula (I)) by performing mono-hydrolysis on long-chain aliphatic dicarboxylic acid di-tert-butyl ester:
which is prepared from a compound of formula (II)
Is prepared by single hydrolysis under the condition of alkaline reagent, wherein n is an integer within 8-18.
In some embodiments, n is an even number within 8-18.
In other embodiments, n is 16 or 18.
In other embodiments, the alkaline agent is barium hydroxide or a hydrate thereof, preferably barium hydroxide octahydrate; the molar ratio of the alkaline agent to the compound of formula (II) is 1-3: 1, preferably 2: 1.
In other embodiments, the reaction solvent is methanol or a mixed solvent of methanol and t-butanol.
In other embodiments, the reaction solvent is a mixed solvent of methanol and tert-butyl alcohol, and the volume ratio of tert-butyl alcohol to methanol is 1-1.2: 1.
In other embodiments, the reaction temperature is 25 to 50 ℃, preferably 28 to 30 ℃.
When n is an even number, the compound of formula (II) can be prepared by:
esterifying the compound of the formula (III) in trifluoroacetic anhydride and tert-butyl alcohol to obtain a compound of a formula (IV),
the compound of the formula (IV) is subjected to coupling reaction under the conditions of nickel chloride hexahydrate, 2', 6', 2' -terpyridine and zinc powder to prepare a compound of a formula (II),
alternatively, the compound of formula (II) may also be prepared by:
the compound of the formula (III) is subjected to coupling reaction under the conditions of nickel chloride hexahydrate, 2', 6', 2' -terpyridine and zinc powder to prepare a compound of a formula (V),
esterifying the compound of formula (V) under the conditions of trifluoroacetic anhydride and tert-butyl alcohol to obtain a compound of formula (II),
when n is an odd number, the compound of formula (II) can be obtained by esterification of its corresponding diacid with trifluoroacetic anhydride, tert-butanol.
The invention provides a novel method for synthesizing long-chain aliphatic dicarboxylic acid mono-tert-butyl ester by controlling the reaction conditions of single hydrolysis, so that the conversion rate of a single hydrolysis target product can reach more than 80%, the single-step reaction yield is more than 70%, the product purity can reach more than 99%, the product is amplified to a kilogram scale, the raw material cost is low, the post-treatment method is simple, column chromatography and other operations are not needed, and the method is suitable for industrial production.
Detailed Description
EXAMPLE 1 preparation of mono-tert-butyl eicosanedioate
The method comprises the following steps: preparation of tert-butyl 10-bromodecanoate
10-bromodecanoic acid (5.7kg, 1.0eq.) and DCM (22.8L, 4V) were added to the reaction kettle; trifluoroacetic anhydride (10.7kg, 2.2eq.) is added dropwise at 0 ℃, and stirred for 0.5 h; t-BuOH (5.89kg,3.5eq.) is added at 0-10 ℃ and stirring is continued for 2 h. Water was added to quench, the mixture was left to stand for liquid separation, and the organic phase was washed with water (4 V.times.5) and concentrated to obtain 6.914kg of a dark brown liquid with a purity of 98.9% and a yield of 98%.
Step two: preparation of ditertiary butyl eicosanedioate
Under the protection of nitrogen, adding 10-bromodecanoic acid tert-butyl ester (6.79kg, 1.0eq.), zinc powder (1.52kg, 1.05eq.) and DMF (26L) into a reaction kettle; adding NiCl2.6H2O (105.1g, 0.02eq.) and 2,2':6', 2' -terpyridine (103.1g, 0.02eq.) were stirred at 35-45 ℃ for 10 h. Dripping 1.8M HCl (20L) at 25-30 ℃, and stirring for 2-4 h; filtering, washing with water (0.5V) and drying to obtain 9.95kg of off-white solid with the purity of 94.9 percent and the yield of 99 percent.
Step three: preparation of mono-tert-butyl eicosanedioate
A general reaction of Ba (OH)2.8H2O (3.1kg, 1.8eq.), di-tert-butyl didecanedioate (2.5kg, 1.0eq.), tert-butanol (45L) and methanol (37.5L) were added to the reactor and stirred at 28-30 ℃ for 30 h. And (3) performing centrifugal filtration, adding the filter cake and toluene (20V) into the reactor, stirring for 2h, adding 1M HCl (10V) and water (10V), separating and concentrating an organic phase into yellow solid, washing with methanol (20L), filtering and drying to obtain 1698g of white solid with the purity of 99.1% and the yield of 77.5%.
EXAMPLE 2 preparation of mono-tert-butyl octadecanedioate
The method comprises the following steps: preparation of octadecanedioic acid
Under the protection of nitrogen, 9-bromononanoic acid (1.29kg, 5.44mol, 1.0eq.) and zinc powder (730g, 2.05eq.) were added to a reaction kettle together with DMF (26L); adding NiCl2.6H2O (65g, 0.05eq.) and 2,2':6', 2' -terpyridine (63.4g, 0.05eq.) were stirred at 35-45 ℃ for 8 h. Dripping 1.8M HCl (20L) at 25-30 ℃, and stirring for 2-4 h; filtering, washing with water (0.5V) and drying to obtain 1.7kg of white solid with the purity of 95.4% and the yield of 99%.
Step two: preparation of di-tert-butyl octadecanedioate
Octadecanedioic acid (1.69kg, 1.0eq.) and THF (9L, 5.3V) were added to the reaction kettle; trifluoroacetic anhydride (3.39kg, 3.0eq.) was added dropwise at 0 ℃, stirred for 1h, and t-BuOH (1.91kg, 4.8eq.) was added dropwise at 0-10 ℃. Stirring for 5h at 25-28 ℃. NaHCO is added3(2.7kg, 6.0eq.) and water (20L, 12V); dropwise adding NaHCO3 aqueous solution into the reaction kettle, and stirring at 15-20 DEG C1 h; filtering and drying to obtain 2.13kg of light yellow solid with the yield of 92.9 percent. Step three: preparation of mono-tert-butyl octadecanedioate
A general reaction of Ba (OH)2.8H2O (2.95kg,1.7eq.), di-tert-butyl octadecanedioate (2.34kg,1.0eq.), tert-butanol (25L) and methanol (25L) were added to the reaction vessel, and stirred at 28-30 ℃ for 20 hours. Centrifuging and filtering, adding the filter cake and toluene (20V) into a reactor, stirring for 2h, adding 1M HCl (10V) and water (10V), separating and concentrating an organic phase into yellow solid, washing with methanol (20L), filtering and drying to obtain 1448g of white solid with the purity of 99.5% and the yield of 71.0%.
Example 3 Single hydrolysis Condition screening experiment
Referring to the procedure of step three of example 1, the results of screening for the conditions of the single hydrolysis reaction are shown in Table 1.
TABLE 1
Claims (10)
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2024232593A1 (en) * | 2023-05-10 | 2024-11-14 | 주식회사 아미노로직스 | Method for preparing mono-tert-butyl-esterified saturated hydrocarbon, and cyclic preparation method therefor |
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|---|---|---|---|---|
| CN101466679A (en) * | 2006-03-30 | 2009-06-24 | 田边三菱制药株式会社 | A process for preparing tetrahydroquinoline derivatives |
| CN109776323A (en) * | 2019-01-28 | 2019-05-21 | 富乐马鸿凯（大连）医药有限公司 | A kind of method that efficient selective prepares the fat diacid list tert-butyl ester |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101466679A (en) * | 2006-03-30 | 2009-06-24 | 田边三菱制药株式会社 | A process for preparing tetrahydroquinoline derivatives |
| CN109776323A (en) * | 2019-01-28 | 2019-05-21 | 富乐马鸿凯（大连）医药有限公司 | A kind of method that efficient selective prepares the fat diacid list tert-butyl ester |
Non-Patent Citations (1)
| Title |
|---|
| HEI MAN CHENG 等: "En Route to a Molecular Sheaf: Active Metal Template Synthesis of a [3]Rotaxane with Two Axles Threaded through One Ring" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2024232593A1 (en) * | 2023-05-10 | 2024-11-14 | 주식회사 아미노로직스 | Method for preparing mono-tert-butyl-esterified saturated hydrocarbon, and cyclic preparation method therefor |
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