Diisopropylethylamine → tert-Butyl[(1R,2R)-2-{[(4-bromo-5 ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamate

Participants

Reaction Steps

4-Bromo-5-ethylthiophene-2-carboxylic acid (1.00 g, 4.25 mmol) and BOP (5.64 g, 12.8 mmol) were dissolved in DMF (42.5 mL) and stirred at room temperature for 5 min. To the reaction solution was added tert-butyl [(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (1.07 g, 4.25 mmol) and diisopropylethyl amine (1.11 mL, 6.38 mmol) and the reaction stirred at room temperature for 64 h. The reaction mixture was diluted with ethyl acetate and washed with water 3×. The organic layer was collected, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0-50% EtOAc/Hex) to give the title compound (1.56 g, 3.34 mmol). LRMS (APCI) calc'd for (C18H25BrF2N2O3S) [M+H]+, 467.1; found 466.9. 1H NMR (CDCl3, 500 MHz) δ 7.32 (s, 1H), 6.28 (s, 1H), 4.90 (s, 1H), 4.54 (s, 1H), 4.29 (s, 1H), 2.81 (q, J=7.5, 2H), 2.22 (m, 1H), 1.88 (m, 1H), 1.81 (m, 1H), 1.69 (m, 1H), 1.59 (m, 1H), 1.46 (s, 9H), 1.41 (m, 1H), 1.28 (t, J=7.3, 3H)

Provenance & Evidence