Imidazole → 2-(Tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanol

Participants

Reaction Steps

In a 250 mL round-bottomed flask (t=g) was added 5-(2,3-difluorophenyl)cycloheptane-1,2-diol (1.454 g, 6.0 mmol) (crude material, azeotroped with dry benzene) in DMF (20 mL) to give a colorless solution. TBS-Cl (0.995 g, 6.60 mmol) and imidazole (0.980 g, 14.40 mmol) were added, and the mixture was stirred at room temperature for 5 hours. TLC (2/1 hexane/EtOAc) indicated complete conversion to two main spots. It was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried with Na2SO4 and concentrated to a colorless oil. Purification by FCC up to 30% EtOAc/hexane afforded the desired mono-protected product as a broad peak. The product fractions were pooled and concentrated to a colorless oil (1.79 g, 84% for two steps). 1H NMR (400 MHz, CDCl3) δ 7.02-6.85 (m, 3H), 3.98-3.70 (m, 2H), 3.18-3.02 (m, 1H), 2.15-1.82 (m, 4H), 1.80-1.45 (m, 4H), 0.91 (s, 9H), 0.90 (2 s, 6H).

Provenance & Evidence