Preparation method of chiral intermediate cyclohexane dimethanol

A technology of cyclohexanedimethanol and chiral intermediate, applied in the field of medicine, can solve the problems of high cost, large amount of red aluminum, unfavorable industrial production, etc., and achieves the effects of low price and stable properties

Inactive Publication Date: 2013-03-06
TIANJIN INSTITUTE OF PHARMA RESEARCH
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  • Abstract
  • Description
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Problems solved by technology

[0004] Japanese patent JP2004-224764 reported the preparation method of 1R, 2R-cyclohexanedimethanol: using 1R, 2R-cyclohexanedicarboxylic acid as raw material, using red aluminum solution as reducing agent to obtain the target compound, the amount of red aluminum used in this method Large, about 5g of red aluminum solution is needed to reduce 1g of 1R, 2R-cyclohexanedicarboxylic acid, which is expensive and unfavorable for industrial production

Method used

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  • Preparation method of chiral intermediate cyclohexane dimethanol
  • Preparation method of chiral intermediate cyclohexane dimethanol
  • Preparation method of chiral intermediate cyclohexane dimethanol

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Embodiment 1

[0014] Dissolve 17.2 g (0.1 mol) of 1R, 2R-cyclohexanedicarboxylic acid in 340 ml of tetrahydrofuran, add 3.8 g (0.1 mol) of sodium borohydride, and 14.5 g (0.1 mol) of boron trifluoride diethyl ether (content 47%) , slowly heated to 70°C for reflux reaction for 3 hours, recovered tetrahydrofuran under reduced pressure, evaporated to dryness, added dropwise aqueous sodium hydroxide solution, adjusted pH = 11, filtered, extracted the filtrate with ethyl acetate three times, combined the ethyl ester solution, and washed with brine , dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness to obtain 14 g of 1R, 2R-cyclohexanedimethanol.

[0015] 1 H-NMR (CDCl 3 )δ: 0.95-1.32 (m, 6H), 1.57-1.74 (m, 4H), 3.38-3.59 (m, 6H). (See figure 2 )

Embodiment 2

[0017] Dissolve 17.2 g (0.1 mol) of 1R, 2R-cyclohexanedicarboxylic acid in 680 ml of ether, add 15.2 g (0.4 mol) of sodium borohydride, and 145 g (1 mol) of boron trifluoride ether (content 47%), at room temperature React for 10 hours, recover tetrahydrofuran under reduced pressure, evaporate to dryness, add aqueous sodium hydroxide solution dropwise, adjust pH=11, filter, and extract the filtrate with ethyl acetate three times, combine the ethyl acetate solution, wash with brine, and dry over anhydrous magnesium sulfate. Filter and evaporate to dryness to obtain 13.5 g of 1R, 2R-cyclohexanedimethanol.

[0018] 1 H-NMR (CDCl 3 )δ: 0.95-1.32 (m, 6H), 1.57-1.74 (m, 4H), 3.38-3.59 (m, 6H). (See figure 2 )

Embodiment 3

[0020] 17.2 g (0.1 mol) of 1R, 2R-cyclohexanedicarboxylic acid was dissolved in 340 ml of tetrahydrofuran, and 54 g (1 mol) of potassium borohydride and 72.5 g (0.5 mol) of boron trifluoride diethyl ether (content 47%) were added successively, keeping React at 10°C for 15 hours, recover tetrahydrofuran under reduced pressure, evaporate to dryness, add aqueous sodium hydroxide solution dropwise, adjust pH=11, filter, extract the filtrate with ethyl acetate three times, combine the ethyl acetate solution, wash with brine, and anhydrous magnesium sulfate Dry, filter, and evaporate to dryness to obtain 13.5 g of 1R, 2R-cyclohexanedimethanol.

[0021] 1 H-NMR (CDCl 3 )δ: 0.95-1.32 (m, 6H), 1.57-1.74 (m, 4H), 3.38-3.59 (m, 6H). (See figure 2 )

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Abstract

The invention belongs to the technical field of medicine, and specifically relates to a preparation method of a chiral intermediate 1R,2R-cyclohexane dimethanol. The chiral intermediate 1R,2R-cyclohexane dimethanol is an important intermediate of an antischizophrinic medicine lurasidone. Lurasidone has substantially treatment effects against both positive and negative symptoms of mental patients. A reduction agent adopted by the invention has low cost and stable property. The preparation method is suitable for industrialized productions.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of a chiral medicine intermediate 1R, 2R-cyclohexanedimethanol. Background technique [0002] The chiral compound 1R, 2R-cyclohexanedimethanol (I) is an important intermediate of the anti-schizophrenia drug Lurasidone. Lurasidone is a dual-action antipsychotic drug, which has high affinity for both 5-HT2 receptors and dopamine D2 receptors, and has a significant effect on both positive and negative symptoms of psychosis. [0003] [0004] Japanese patent JP2004-224764 reported the preparation method of 1R, 2R-cyclohexanedimethanol: using 1R, 2R-cyclohexanedicarboxylic acid as raw material, using red aluminum solution as reducing agent to obtain the target compound, the amount of red aluminum used in this method Large, the reduction of 1g of 1R, 2R-cyclohexanedicarboxylic acid requires about 5g of red aluminum solution, which is expensive and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C31/27C07C29/147
Inventor 陈蔚潘毅康江鹏陶勇程玉红
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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