Citric Acid → 2-[3(S)-(tert-butoxycarbonyl)amino-5(S)-(p-tert-butyl-benzyl)-2(S)-hydroxy-6-methyl-heptyl]-N-butyl-acrylamide

Participants

Reaction Conditions

Reaction Steps

695 mg of methacrylic acid butylamide are dissolved in 30 ml of tetrahydrofuran and, at -75° C., 6.2 ml of 1.6M n-butyllithium in hexane are added thereto. The reaction mixture is stirred for 30 minutes at 0° C. and then, at -75° C., 9.8 ml of 1M chlorotitanium triisopropoxide in hexane are added thereto. The mixture is stirred for a further 15 minutes at -75° C. and then, at the same temperature, a solution of 924 mg of 2(S)-tert-butoxy-carbonyl-amino-4(S)-isopropyl-5-(p-tert-butyl-phenyl)-pentanal in 10 ml of tetrahydrofuran is added dropwise thereto. The reaction mixture is then stirred further for 15 minutes at -75° C. and for 70 minutes at 0° C. and then, in succession, 15 ml of 10% aqueous citric acid solution, water and diethyl ether are added thereto. The product is extracted repeatedly with diethyl ether. The diastereoisomeric mixture is separated by FC (700 g of silica gel, eluant: dichloromethane/diethyl ether=9:1). The title compound is obtained: diastereoisomer I: Rf (dichloromethane/diethyl ether=9:1)=0.21; diastereoisomer II: Rf (dichloromethane/diethyl ether=9:1)=0.14.

Provenance & Evidence