Process for the synthesis of chirally pure beta-amino-alcohols

• Main Authors: Kreft, Anthony, Antane, Madelene, Cecil Cole, Derek, Kubrak, Dennis, Resnick, Lynn, Stock, Joseph, Wang, Zheng
• Format: Patent
• Language: English
• Published: 31.07.2003

A process is provided for preparing chirally pure S-enantiomers of -amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the formula (R) 2 CH(CH 2 ) n CH 2 X; b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid; c) activating the carboxylic acid with an acid chloride, phosphorus trichloride, acid anhydride, or thionyl chloride in the presence of a tertiary amine base; d) reacting the product of step c) with an alkali metal salt of S-4-benzyl-2-oxazolidinone; e) treating the product of step d) with a strong non-nucleophilic base to form an enolate anion; f) trapping the enolate anion with 2,4,6-triisopropylbenzenesulfonyl azide to afford an oxazolidinone azide; g) hydrolyzing the oxazolidinone azide with an aqueous base to afford an -azido acid; h) reducing the -azido acid to the -amino acid; and i) recrystallizing the -amino acid to the chirally pure -amino acid. A process is also provided for preparing chirally pure S-enantiomers of -amino alcohols further comprising the steps of reducing the crude -amino acid to the -amino alcohol and recrystallizing the -amino alcohol to the chirally pure -amino alcohol. A process is further provided for preparing chirally pure S enantiomers of N-sulfonyl -amino alcohols further comprising the steps of sulfonylating the -amino alcohol with 5-chloro-thiophene-2-sulfonyl halide; and recrystallizing to afford the chirally pure N-sulfonyl -amino alcohols.