Diisopropylethylamine → 9H-Fluoren-9-ylmethyl[(1S,2R)-2-{[(4-bromo-5-ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamate

Participants

Reaction Steps

4-Bromo-5-ethylthiophene-2-carboxylic acid (300 mg, 1.15 mmol) and BOP (762 mg, 1.72 mmol) were dissolved in DMF (11.5 mL) and stirred at room temperature for 5 minutes. (1R,6S)-6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-difluorocyclohexanaminium chloride (432 mg, 1.16 mmol) was added followed by diisopropylethyl amine (0.50 mL, 2.87 mmol) and the solution was stirred at room temperature for 18 h. The solution was diluted with water, and extracted with dichloromethane (×3). The organic layers were collected, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography affording the title compound as an orange oil. 1H NMR (500 MHz, CDCl3) δ 7.72 (d, 2H); 7.46 (dd, 2H); 7.36 (s, 1H); 7.35 (d, 2H); 7.23 (dd, 2H); 6.36 (d, 1H); 5.14 (d, 1H); 4.36 (dd, 1H); 4.29 (dd, 1H); 4.13 (dd, 1H); 4.01 (dd, 1H); 3.86 (dd, 1H); 2.70 (q, 2H); 2.82 (m, 1H); 2.17 (m, 1H); 1.86 (m, 2H); 1.65 (m, 1H); 1.43 (m, 1H); 1.18 (t, 3H). LRMS (APCI) calc'd for (C28H27BrF2N2O3S) [M+H]+, 589.1. found 589.1.

Provenance & Evidence