Sulfuric Acid → (S)-2-Hydroxymethyl-azetidine-1-carboxylic acid benzyl ester

Participants

Reaction Steps

This solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (2.00 g, 24.0 mmol) was then added, and benzyloxycarbonyl chloride (4.00 g, 24.0 mmol) was added thereto at room temperature. The mixture was then stirred for 14 hours. The solution was adjusted to pH 7, and extracted with ethyl acetate (50 mL×2). The extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate (1/1) as a mobile phase. This separation/purification gave (S)-N-benzyloxycarbonylazetidine-2-methanol (2.01 g, yield 91.0%). The yield was improved as compared with that obtained in Example 1 (69.1%). The formation of the byproduct (S)-2-N-benzyloxycarbonyl-1,4-butanediol decreased to a yield of 7.0% (0.17 g).

Provenance & Evidence