Method of preparing R-(+)-3-chlorophenylpropanol

A kind of technology of chlorophenylpropanol and chloropropiophenone, which is applied in the field of preparation of R-(+)-3-chlorophenylpropanol

Active Publication Date: 2007-08-08
XIAMEN FUMAN PHARMA +1
View PDF4 Cites 21 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0023] However, the single-rotation of 3-chlorophenylpropanol still needs to be obtained by resolution in the above method, and the waste single-rotation of 3-chlorophenylpropanol will still be produced.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method of preparing R-(+)-3-chlorophenylpropanol
  • Method of preparing R-(+)-3-chlorophenylpropanol
  • Method of preparing R-(+)-3-chlorophenylpropanol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] Take dimethyl sulfoxide 200mL, S-(-)-N, N-dimethyl-α, α-diisopropylisoleucinol 30g, NaBH 4 Add 9g into the three-necked flask, then add 100mL of dimethyl sulfoxide containing 28g of anhydrous zinc chloride, stir evenly, take 34g of 3-chloropropiophenone at 25-30°C and add in batches, raise the temperature to reflux, and react 14h, cooled to room temperature, filtered to remove the filter residue, heated the filtrate and evaporated to dryness and recovered the solvent, then added 300mL of dichloroethane, cooled to 0°C, kept warm for crystallization for 8h, filtered to obtain R-(+)-3-Chlorobenzene About 18 g of the crude propanol solid was recrystallized from 250 mL of dichloroethane to obtain 11 g of R-(+)-3-chlorophenylpropanol solid.

[0076] The melting point mp of the obtained R-(+)-3-chlorophenylpropanol is 56~57°C, and the optical rotation α 19 =+25°.

Embodiment 2

[0078] Dimethyl sulfoxide 350mL, S-(-)-N, N-dimethyl-α-p-tolylisoleucinol 35g, NaBH 4 Add 10g, 15g of anhydrous zinc chloride, and 35g of 3-chloropropiophenone into the three-necked flask together, stir evenly, heat up to reflux, react for 24h, cool to room temperature, filter to remove the filter residue, add 100mL of 5mol / L NaOH solution to the filtrate and water 300mL, stirred and reacted at 40°C for 1h, stood to separate layers, separated the water layer, evaporated the solvent layer to dryness and recovered the solvent, released the residue while hot, and obtained R-(+)-3-chloro The crude product of phenylpropanol is about 30 g, and the crude product is recrystallized with anhydrous isopropanol to obtain about 23 g of refined product R-(+)-3-chlorophenylpropanol, and the yield is about 68% to 73%.

[0079] The melting point mp of the obtained R-(+)-3-chlorophenylpropanol is 57~59° C., and the optical rotation α 19 =+25°.

Embodiment 3

[0081] First add 18g of anhydrous tin chloride to 200mL of tetrahydrofuran to prepare suspension A for later use. Take tetrahydrofuran 150mL, S-(-)-N-methyl-N-ethyl-α-methyl-α-ethylisoleucinol 37.8g, KBH 4 Add 15g and 21g of 3-chloropropiophenone into a three-necked flask, stir evenly, heat up to 40°C, add suspension A, heat up and reflux for 18 hours while stirring, after the reaction is complete, cool to 40°C, filter to remove the filter residue. After the filtrate was heated up and evaporated to dryness and the solvent tetrahydrofuran was recovered, 400mL of n-hexane was added, heated until transparent, then cooled to 5°C, kept for crystallization for 3h, and filtered to obtain solid crude product of R-(+)-3-chlorophenylpropanol. After recrystallization from 250 mL of isopropanol, about 8 g of white solid R-(+)-3-chlorophenylpropanol was obtained.

[0082] The melting point mp of the obtained R-(+)-3-chlorophenylpropanol is 58~60°C, and the optical rotation α 19 =+25°, th...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
optical rotationaaaaaaaaaa
optical rotationaaaaaaaaaa
melting pointaaaaaaaaaa
Login to view more

Abstract

The invention discloses a making method of R-(+)-3-chlophenicol, which is characterized by the following: adopting left-handed bulk of chiral amino acid derivant as catalyst; synthesizing 3-chlophenicol and NaBH4 or KBH4 directly to produce R-(+)-3-chlophenicol; selecting the left-handed bulk from one of left-handed isoleucine derivant, left-handed proline derivant, left-handed tryptophan derivant, left-handed cysteine derivant, left-handed histidine derivant and left-handed methionine derivant.

Description

technical field [0001] The invention relates to a preparation method of a useful intermediate 3-chloropropanol which can be used as a drug for treating depression, in particular to a preparation method of its single body R-(+)-3-chloropropanol. Background technique [0002] Dapoxetine, chemical name S-(+)-N,N-dimethyl-α-[2-(naphthyloxy)ethyl]benzylamine hydrochloride (N,N-dimethyl- α-[2-(naphthalenyloxy)ethyl]benyenemethanamine hydrochloride), is a selective serotonin reuptake inhibitor, which can be used for the treatment of depression, alcoholism, weight loss, amnesia and other diseases, for forgetfulness, irritability, depression, Aloof and effective, it is also the world's first oral drug for the treatment of premature ejaculation in men. The drug is a selective serotonin uptake inhibitor and has no direct effect on neuronal receptors. Since this class of drugs does not effectively inhibit other monoamines, less side effects are expected after administration. [0003]...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07C29/143C07C33/46C07B53/00B01J31/04
Inventor 陈天度曹丽陈品岗
Owner XIAMEN FUMAN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap