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Process for the preparation of diisopinocampheylchloroborane

A technology for pinenyl chloroborane and diisopine, which is applied in the field of preparing diisopinepine pinyl chloroborane from Lewis acid, can solve problems such as high risk, unsafe industrial production, and toxicity, and reduce production costs. , the effect of reducing hidden dangers in production

Inactive Publication Date: 2008-07-23
SHANGHAI ACEBRIGHT PHARMA GRP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The shortcoming of this method: the one, the boron source of this method contains dimethyl sulfide, and the smell of this compound is very unpleasant; The product also needs to be separated; the third is that only when the optical purity of the raw material α-pinene is greater than 90%, the optical purity of diisopine pinaneyl chloride borane may reach more than 99%
The main disadvantage of this method is that boron trichloride gas is used. This gas not only has a strong pungent odor, but also is toxic and highly dangerous. It will decompose explosively when it encounters water. It is extremely unsafe for industrial production and is expensive for gas transportation. The cost is also quite high

Method used

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  • Process for the preparation of diisopinocampheylchloroborane
  • Process for the preparation of diisopinocampheylchloroborane
  • Process for the preparation of diisopinocampheylchloroborane

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The preparation of diisopine pinocampyl chloride borane:

[0035] 1.14g (30mmol) NaBH 4 Add to the three-necked bottle, add 30ml ethylene glycol dimethyl ether, 28.8ml (180mmol) (1R)-(+)-α-pinene (ee.50%; [α] 20 D , neat: +27.4°). Add 7.5ml (60mmol) BF dropwise under stirring at -10°C 3 ·Et 2 O, about 30 minutes to drop. Raised to 0°C and stirred for 4 hours (the liquid was a milky white viscous liquid). Add 7.4g (35.5mmol) PCl at 0°C 5 , raised to 100°C and stirred for 3 hours, the solution was left to cool naturally, and then directly entered into the next step of reaction. The molar concentration of diisopinocampylchloroborane is 1M.

[0036] Chiral reduction:

[0037] Dissolve 1.5 g (3.3 mmol) of methyl 2-(3-(3-(2-(7-chloro-2-quinolyl) vinyl) phenyl) 3-oxopropyl) benzoate in 30 ml of THF , Add the obtained catalyst solution under stirring at -15°C, and stop the refrigeration after stirring for 8 hours. Slowly add 31% K in a water bath 2 CO 3 The aqueous...

Embodiment 2

[0039] The preparation of diisopine pinocampyl chloride borane:

[0040] 1.14g (30mmol) NaBH 4 Add to the three-necked flask, add 30ml ethylene glycol dimethyl ether, 19.2ml (120mmol) (1R)-(+)-α-pinene (ee.65%; [α] 20 D , neat: +27.4°). Add 6ml (48mmol) BF dropwise under stirring at -10°C 3 ·Et 2 O, about 30 minutes to drop. Raised to 0°C and stirred for 4 hours (the liquid was a milky white viscous liquid). Add 7.4g (35.5mmol) PCl at 0°C 5 , raised to 80°C and stirred for 1 hour, the solution was left to cool naturally, and then directly entered into the next step of reaction. The molar concentration of diisopinocampylchloroborane is 1M.

[0041] Chiral reduction:

[0042] Dissolve 5 g (11 mmol) of methyl 2-(3-(3-(2-(7-chloro-2-quinolyl) vinyl) phenyl) 3-oxopropyl) benzoate in 85 ml THF, - The obtained catalyst solution was added under stirring at 16°C, and after stirring for 8 hours, the refrigeration was stopped. Slowly add 31% K in a water bath 2 CO 3 The aque...

Embodiment 3

[0044] The preparation of diisopine pinocampyl chloride borane:

[0045] 760mg (20mmol) NaBH 4 Add in the three-necked flask, add 20ml ethylene glycol dimethyl ether, 6.4ml (40mmol) (1s)-(-)-α-pinene (ee.>80%; [α] 20 D : -45°). Add 4ml (32mmol) BF dropwise under stirring at -10°C 3 ·Et 2 O, about 30 minutes to drop. Warm to 0°C and stir for 5 hours. Add 4.9g (24mmol) PCl at 0°C 5, raised to 85°C and stirred for 0.5 hours, the solution was left to cool naturally, and then it could directly enter the next step of reaction. Molar concentration of diisopinocampylchloroborane at 1 M chiral reduction:

[0046] 9g (20mmol) 2-(3-(3-(2-(7-chloro-2-quinolyl) vinyl) phenyl) 3-oxopropyl) methyl benzoate was dissolved in 100ml THF,- The obtained catalyst solution was added under stirring at 24°C, and after stirring for 9 hours, the refrigeration was stopped. Slowly add 31% K in a water bath 2 CO 3 The aqueous solution is about 40ml, and the pH is neutralized to 7. The organic ...

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Abstract

The invention discloses a new low-cost preparation method of B-Chlorodiisopinocampheylborane, which comprises the reaction of sodium borohydride and a-pinene and phosphorus pentachloride. The new low-cost preparation method of B-Chlorodiisopinocampheylborane has the advantages that the mixture with the gotten B-Chlorodiisopinocampheylborane can be directly used for the reduction from prochiral ketones to the corresponding chiral alcohols with high optical purity, and the production cost and hidden danger are greatly reduced.

Description

technical field [0001] The invention relates to a new method for preparing diisopinepinocampylchloroborane, in particular to a method for preparing diisopinepinocampylchloroborane with Lewis acid. Background technique [0002] As we all know, diisopine pinocampyl chloride borane is a chiral reducing agent with strong reducing ability and difficult to prepare. There are mainly two kinds of preparation methods reported: one is the method reported in US 5,043,479: first refer to Document J.Org.Chem.1982, 47, 5065, uses α-pinene and dimethyl sulfide borane to prepare intermediate diisopine pinocampyl borane, and then reacts with hydrogen chloride gas to generate The product is diisopine pinocampyl chloride borane, and the latter needs to be crystallized and separated before being used for the chiral reduction of ketones. The shortcoming of this method: the one, the boron source of this method contains dimethyl sulfide, and the smell of this compound is very unpleasant; The 2nd,...

Claims

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Application Information

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IPC IPC(8): C07F5/02C07D215/14C07B53/00C07B35/02
CPCY02P20/55
Inventor 李金亮丁奎岭吴江
Owner SHANGHAI ACEBRIGHT PHARMA GRP
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