Lithium Hydroxide → (2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid

Participants

Reaction Conditions

Reaction Steps

Into the THF solution of 2-(4-chloro-2,3-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (771 mg, 2.81 mmol) was added 1.0 M K3PO4 (7.02 mL), ethyl (2R)-4-(4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (1000 mg, 2.34 mmol) and Pd(II)dppf.DCM (90 mg, 0.117 mmol, 5 mol %). The reaction mixture was stirred for 1 h at 65° C. To the reaction mixture was then added a solution of LiOH (168 mg, 7.02 mmol) in water (7.5 mL). The reaction mixture was stirred for 45 min at 55° C. The reaction mixture was treated with 1 N NaOH (4 mL) and the aqueous layer was separated and adjusted to a pH of 2 with 3 N HCl. A precipitate formed and was collected by filtration and washed with EtOAc to give the title compound as an off-white solid (0.88 g, 89.6%) LCMS m/z 420.0 (M+1). 1H NMR ppm 1.58 (s, 3 H) 2.20 (ddd, J=13.12, 10.68, 4.88 Hz, 1 H) 2.40-2.48 (m, 1 H) 3.17 (s, 3 H) 3.95 (ddd, J=12.54, 10.88, 5.66 Hz, 1 H) 4.10 (ddd, J=12.63, 10.78, 4.88 Hz, 1 H) 6.47 (dt, J=7.02, 1.85 Hz, 1 H) 6.58-6.61 (m, 1 H) 7.42-7.49 (m, 1 H) 7.52-7.58 (m, 1 H) 7.81 (d, J=7.02 Hz, 1 H).

Provenance & Evidence