Triphenylphosphine → HCID 68569280, compound

Participants

Reaction Steps

To a slurry of methyl 3-{[(1R)-1-(2-chloro-3-hydroxyphenyl)ethyl]oxy}-5-{5-[(trifluoromethyl)oxy]-1H-benzimidazol-1-yl}-2-thiophenecarboxylate (Intermediate 25, 0.18 g, 0.35 mmol) and 1-methyl-4-piperidinol (0.12 g, 1.1 mmol) in DCM (10 mL) was added triphenylphosphine (0.18 g, 0.70 mmol) and di-tert-butyl azodicarboxylate (0.16 g, 0.70 mmol). The clear, yellow solution was stirred for 1 h, and then silica gel (3 g) was added. The volatiles were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 100% 80/20/1 DCM/MeOH/ammonium hydroxide:DCM) to give 0.20 g (0.34 mmol) of methyl 3-[((1R)-1-{2-chloro-3-[(1-methyl-4-piperidinyl)oxy]phenyl}ethyl)oxy]-5-{5-[(trifluoromethyl)oxy]-1H-benzimidazol-1-yl}-2-thiophenecarboxylate which was then dissolved in a solution of 7 N ammonia in MeOH (10 mL). The mixture was heated in a sealed tube to 80° C. for 40 h and then cooled to rt. Silica (1 g) was added, the volatiles were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 100% 80/20/1 DCM/MeOH/ammonium hydroxide:DCM) to afford 0.18 g (86%) of the title compound as a light yellow solid. 1H NMR (400 MHz, CD3OD): δ 8.45 (s, 1H), 7.63 (s, 1H), 7.45 (d, J=8.79 Hz, 1H), 7.31 (m, 2H), 7.17 (d, J=7.51 Hz, 1H), 7.10 (d, J=8.24 Hz, 1H), 6.97 (s, 1H), 6.05 (q, J=6.29 Hz, 1H), 4.56 (m, 3H), 2.72 (br m, 2H), 2.47 (br m, 2H), 2.33 (s, 3H), 1.95 (br m, 4H), 1.77 (d, J=6.41 Hz, 3H): MS (ESI): 595 [M+H]+.

Provenance & Evidence