Methyl {4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}(oxo)acetate → 1-{4-[({6-[2-Fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}-3,3-dimethyl-1-oxo-2-butanone

Participants

Reaction Conditions

Reaction Steps

A solution of methyl {4-[({6-[2-fluoro-4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinyl}(oxo)acetate (Example 137, 95 mg, 0.21 mmol) in THF (4 mL) at −78° C. was treated with tert-butylmagnesium chloride (1M in THF, 0.26 mL, 0.26 mmol). The mixture was stirred at −78° C. for 3 h. Additional tert-butylmagnesium chloride (1M in THF, 0.22 mL, 0.22 mmol) was added. The mixture was stirred at −78° C. for 3 h. More tert-butylmagnesium chloride (1M in THF, 0.25 mL, 0.25 mmol) was added. The reaction mixture was stirred at −78° C. for 1 h, quenched with saturated aqueous NH4Cl and extracted with EtOAc (50 mL×2). The combined organic extracts were washed with brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a viscous light brown oil. The crude material was purified by flash chromatography on a silica gel column eluted with 1:10 acetone/CH2Cl2 to give 50 mg (50%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.42 (d, 1H, J=2.9 Hz), 8.23 (t, 1H, J=7.8 Hz), 7.85-7.77 (m, 2H), 7.73 (dd, 1H, Ja=10.3 Hz, Jb=1.5 Hz), 7.30-7.25 (m, 1H), 4.65-4.55 (m, 1H), 3.95-3.85 (m, 2H), 3.55-3.45 (m, 1H), 3.15-3.05 (m, 4H), 2.80-2.70 (m, 1H), 2.25-2.10 (m, 1H), 2.00-1.85 (m, 2H), 1.50-1.30 (m, 2H), 1.27 (s, 9H); LRMS (ESI), m/z 477 (M+H).

Provenance & Evidence