2,6-Lutidine → HCID 68678071, compound

Participants

Reaction Conditions

Reaction Steps

To a −78° C. solution of benzyl cyclohexyl(hydroxy)acetate (61 mg, 0.25 mmol) and 4A molecular sieves in 1.2 mL CH2Cl2 was added trifluoromethanesulfonic anhydride (0.05 mL, 0.30 mmol). After stirring for 10 min at this temperature, 2,6-lutidine (0.06 mL, 0.49 mmol) was added. After 15 min, diisopropylethylamine (0.09 mL, 0.49 mmol) was added and after another 15 min, a solution of 1-((1R,5S)-8-{2-[4-(3-fluorophenyl)piperidin-4-yl]ethyl}-8-azabicyclo[3.2.1]oct-3-yl)-2-methyl-1H-benzimidazole dihydrochloride (153 mg, 0.30 mmol) in 1 mL CH2Cl2 was added. The reaction mixture was stirred at −78° C., then allowed to warm to room temperature overnight, washed with saturated aqueous NaHCO3, and purified by preparatory TLC using 5% MeOH in CHCl3 to afford benzyl cyclohexyl(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)acetate (33 mg, 20%) as an oil. 1H NMR (400 MHz, CDCl3), δ 7.68-7.64 (m, 1H), 7.33-7.23 (m, 7H), 7.20-7.12 (m, 2H), 7.05 (m, 1H), 6.97 (m, 1H), 6.89 (m, 1H), 5.05 (ABq, 2H, J=12.3 Hz), 4.61 (m, 1H), 3.26-3.18 (m, 2H), 2.92 (d, 1H, J=10.4 Hz), 2.70 (m, 1H), 2.64-2.50 (m, 2H), 2.57 (s, 3H), 2.46-2.30 (m, 3H), 2.12-0.81 (m, 25H); ESI-MS 677 (M+H).

Provenance & Evidence