Preparation of amphetamines from phenylpropanolamines

US6399828B1 · kind B1 · utility

Assignee

• Boehringer Ingelheim Chemicals, Inc. · US

Inventors

• Robert Boswell · Richmond, US
• Young S. Lo · Hockessin, US

Key dates

• Filing date: Oct 29, 2001
• Grant date: Jun 4, 2002
• Expiry date: Oct 29, 2021

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C209/68
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A process for making compound of formula I from a phenylpropanolamine salt of formula II wherein:R1 is hydrogen or a lower alkyl group;each R2 is independently a hydrogen, halogen, lower alkyl group, lower alkoxy groups, lower alkyl group substituted with 1 to 5 halogens, lower alkoxy groups substituted with 1 to 5 halogens, or both R2 together when on adjacent carbons constitute a —O(CH2)xO— where x is 1 to 4, thereby forming a ring structure fused with the phenyl group;R3 is a C1-C8-alkyl group, a C1-C12-aralkyl group, C1-C12-alkaryl group, or a phenyl group, each optionally substituted by 1 to 5 substituents selected from halogen, hydroxy, or C1-C6-alkyl; andHX is an equivalent of an organic or inorganic acid,the process comprising:(a) acylating the phenylpropanolamine salt of formula II with an acylating agent in a solvent at elevated temperature to make a reaction mixture containing an O-acylated phenylpropanolamine salt of formula III which can be isolated by the addition of a crystallization solvent, or optionally this mixture can be used in the next step; and(b) hydrogenating the O-acylated phenylpropanolamine salt to make the compound of formula I in the presen…