Benzyl chloroformate → benzyl N-(4,4,4-trifluoro-1-hydroxybutan-2-yl)carbamate

Participants

Reaction Steps

400 mg of rac-2-amino-4,4,4-trifluorobutan-1-ol (Example 42A, 2.5 mmol, purity about 90%, 1 equivalent) in 36 ml of 1,4-dioxane were admixed at RT with 0.38 ml of 50% aqueous potassium carbonate solution (1.7 mmol, 0.68 equivalent) and 0.54 ml of benzyl chloroformate (3.8 mmol, 1.5 equivalents), and the mixture was stirred at RT for 2 h. Then another 0.11 ml of benzyl chloroformate (0.76 mmol, 0.3 equivalent) and 0.08 ml of 50% aqueous potassium carbonate solution (0.35 mmol, 0.14 equivalent) were added and the mixture was stirred at RT for a further 30 min. Concentration under reduced pressure was followed by purification by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA). The resulting crude product was taken up in ethyl acetate and washed twice with saturated aqueous sodium hydrogencarbonate solution. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were dried over sodium sulphate, filtered and concentrated. 490 mg (70% of theory) of the title compound were obtained.

Provenance & Evidence