Sodium Hydroxide → 1,1-Dimethylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 1,1-dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate (0.781 g, 1.68 mmol), methanesulphinic acid sodium salt (0.86 g, 80%, 6.71 mmol), Cul (1.28 g, 6.71 mmol) and NaOH (81 mg, 2.02 mmol) in DMSO (20 mL) and water (0.5 mL) was degassed, purged with N2 and heated at 110° C. for 48 h. After cooled to ambient temperature, the mixture was poured into water (75 mL) and EtOAc (75 mL), and filtered through Celite®. The solid on Celite® was further washed with EtOAc. The filtrate and washing were combined and transferred to a separatory funnel. The organic layer was separated and washed with water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow solid. The crude product was purified by chromatography on a silica gel column eluted with 25% EtOAc/CH2Cl2 followed by trituration with hot hexanes containing 1% of MeOH to give 0.5 g (64%) of 1,1-dimethylethyl 4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.40 (d, 1H, J=3.0 Hz), 8.15-8.10 (m, 1H), 7.90-7.75 (m, 3H), 7.50 (dd, 1H, Ja=8.8 Hz, Jb=3.0 Hz), 4.20-4.10 (m, 2H), 4.00 (d, 2H, J=6.3 Hz), 3.18 (s, 3H), 2.90-2.75 (m, 2H), 2.15-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.40-1.25 (m, 2H); LRMS (ESI), m/z 465 (M+H).

Provenance & Evidence