Cyclopropylamine → tert-Butyl ((2S,3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

Cyclopropylamine (2.77 g, 48.53 mmol) was dropwise added to an ethyl acetate (108 g) solution of (2S,3S)-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid (10.0 g, 40.44 mmol). The mixture was cooled by ice. A mixed solution of HOBt monohydrate (1.86 g, 12.13 mmol)/THF (9.3 g)/water (1.9 g)=1/5/1 and a mixed solution of EDC hydrochloride (8.53 g, 44.48 mmol)/water (8.5 g)=1/1 were dropwise added in that order, and the mixture was stirred for 14 hours with cooling by ice. Next, 5% NaHCO3 aqueous solution (50 g) was added, and the mixture was heated up to 40° C. Then, the aqueous layer was removed. The organic layer was washed once with 5% NaHCO3 aqueous solution (50 g) at 40° C., and finally washed with water (50 g), to obtain a solution of (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide (reaction yield: 97 mol %, extraction yield: 98 mol %, chemical purity: 96.0 area %).

Provenance & Evidence