1,2-Dichloroethane → (1-Carbamoyl-2-isobutyl-cyclopropylmethyl)-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(tert-butoxycarbonylamino-methyl)-2-isobutyl-cyclopropanecarboxylic acid (5.2 g, 19.2 mmol) in dry THF (190 mL) was added HOBt (2.85 g, 21.1 mmol), NMM (2.32 mL, 21.1 mmol) and EDC (4.0 g, 21.1 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 3 hours and quenched with concentrated ammonium hydroxide (16 mL). The reaction mixture was stirred at room temperature overnight. Excess of solvent was removed in vacuo and the residue was dissolved in EtOAc (200 mL). The organic layer was washed with 1N HCl, aqueous NaHCO3, brine and dried over Na2SO4. Evaporation of excess of solvent gave 3.5 g (69%) of (1-carbamoyl-2-isobutyl-cyclopropylmethyl)-carbamic acid tert-butyl ester as a colorless oil: 1H NMR (300 MHz, CD3OD) & 0.61 (dd, J=4.2, 6.5 Hz, 1H), 0.94 (d, J=5.0 Hz, 3H), 0.96 (d, J=5.0 Hz, 3H), 1.20 (m, 1H), 1.29 (dd, J=3.9, 8.7 Hz, 1H), 1.44 (s, 9H), 1.51 (m, 2H), 1.65 (m, 1H), 3.20 (d, J=15.2 Hz, 1H), 3.54 (d, J=15.2 Hz, 1H); 13C (75 MHz, CD3OD) δ 21.5, 23.2, 23.6, 27.4, 29.3, 30.3, 30.4, 39.3, 41.8, 80.9, 159.3, 179.9; MS (APCI) m/z271 [M+H]+.

Provenance & Evidence