Methyl dichloroacetate → 2-Amino-5-(1-methyl-cyclopropyl)-thiazole-4-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Combine 1-Methyl-cyclopropanecarbaldehyde (4.88 g, 58.01 mmol) and methyldichloroacetate (5.46 mL, 52.74 mmol) in diethyl ether (20 mL); cool to 0° C. Add dropwise a solution of sodium (1.21 g, 52.74 mmol) in methanol (20 mL). Stir the reaction mixture for 4 hours at 0° C. under N2. Extract the mixture with diethyl ether versus water. Dry the resulting organics over magnesium sulfate, filter, and concentrate to a clear liquid. Combine the liquid with thiourea (4.42 g, 58.01 mmol) in methanol (25 mL). Heat the reaction mixture for 14 hours at 60° C. under N2. Concentrate in vacuo and purify on a plug of silica gel, eluting with hexanes→3% methanol in dichloromethane→5% methanol in dichloromethane to afford product (5.10 g, 46% over two steps). MS (ES), m/z 213 (M+1).

Provenance & Evidence