Isobutyl chloroformate → Methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

1-Methoxycarbonylcyclopropane carboxylic acid (16.4 g, 113.89 mmol), TEA (17.6 mL, 127.55 mmol), and THF (325 mL) are charged in a round bottom flask. The mixture is cooled to −10° C. and isobutyl chloroformate (16.5 mL, 127.55 mmol) is added dropwise. The solution is stirred for 1 h. In a separate flask, sodium borohydride (13 g, 341.67 mmol) is dissolved in a mixture of THF (165 mL) and water (40 mL) and cooled in an ice bath. The insoluble material is removed by filtration from the first solution. To the borohydride solution is added the 1-methoxycarbonylcyclopropane carboxylic acid solution described above, dropwise over a period of 1.5 h. The resulting solution is stirred at the same temperature for 1 h. The reaction mixture is poured into a cooled 20% aqueous solution of citric acid and extracted with ethyl acetate (3×150 mL). The combined organic layers are washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to afford the title compound (13.5 g, 91%). 1H NMR (400 MHz, CDCl3); δ 0.9-0.8 (m, 2H), 1.3-1.2 (m, 2H), 3.62 (s, 2H) 3.69 (s, 3H).

Provenance & Evidence