Methanol → 1-Methylethyl 4-[({2-(hydroxymethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

NaBH4 (32 mg, 0.82 mmol) was added to a stirred solution of methyl 3-{[(1-{[(1-methylethyl)oxy]carbonyl}-4-piperidinyl)methyl]oxy}-6-[4-(methylsulfonyl)phenyl]-2-pyridinecarboxylate (Example 135, 0.20 g, 0.41 mmol) in THF (4 mL) at 0° C. MeOH (2 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 2 h, then allowed to warm to ambient temperature and stirred overnight. The mixture was heated at 70° C. for 2 h, more NaBH4 (100 mg, 2.56 mmol) was added. Heating was continued at 70° C. for 2 h, then more NaBH4 (100 mg, 2.56 mmol) was added. The mixture was heated at 70° C. for 2 h, cooled to ambient temperature, quenched with saturated aqueous NH4Cl and extracted with EtOAc (70 mL×2). The combined organic extracts were washed with brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a light brown oil. The crude material was purified by flash chromatography on a silica gel column eluted with 1:8 acetone/CH2Cl2 to give 0.153 g (81%) of 1-methylethyl 4-[({2-(hydroxymethyl)-6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.15 (d, 2H, J=8.5 Hz), 8.02 (d, 2H, J=8.5 Hz), 7.71 (d, 1H, J=8.6 Hz), 7.24 (d, 1H, J=8.6 Hz), 4.93 (septet, 1H, J=6.2 Hz), 4.82 (s, 2H), 4.22 (bs, 2H), 3.91 (d, 2H, J=6.1 Hz), 3.09 (s, 3H), 2.85-2.70 (m, 2H), 2.15-2.00 (m, 1H), 1.90_1.80 (m, 2H), 1.40-1.20 (m, 8H); LRMS (ESI), m/z 463 (M+H).

Provenance & Evidence