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

摘要

Disclosed is a process for preparing chirally pure S-enantiomers of alpha-amino acids comprising the steps of: (a) preparing an organometallic reagent from an alkyl halide of formula (R)2CH(CH2)nCH2X, wherein: X is Cl, Br or I and n is 0 to 10, R is optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, phenyl benzyl, or CH2cycloalkyl, CH2-3-indole, CH-alkyl-2-furan, CH-alkyl-4-methoxyphenyl, CH-alkyl-phenyl, or CH(OH)-4-SCH3-phenyl, (b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid, (c) activating the carboxylic acid with an acid halide, 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) trappinmg 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 alpha-azido acid, (h) reducing the alpha-azido acid to an alpha-amino acid, (i) recrystallising the alpha-amino acid to form the chirally pure alpha-amino acid.