Sodium Bicarbonate → (2,4-Dichloro-pyrimidin-5-yl)-(2,3-difluoro-6-methoxy-phenyl)-methanone

Participants

Reaction Conditions

Reaction Steps

A mixture of rac-(2,4-dichloro-pyrimidin-5-yl)-(2,3-difluoro-6-methoxy-phenyl)-methanol (20.5 g, 63.8 mmol, Example 287) in dichloromethane (180 mL) was chilled with stirring to 0° C. and added water (20 mL), sodium bicarbonate powder (2.42 g, 28.73 mmol, Aldrich), tetrabutylammonium bromide (0.617 g, 1.915 mmol, Aldrich), and 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical (0.1 g, 0.638 mmol, TEMPO, Aldrich). Sodium hypochlorite solution (6.15%, Aldrich) was added portionwise until all starting material was oxidized (TLC ethyl acetate/hexanes 3:1). The cold reaction mixture was then washed with water (2×), dried (MgSO4) and concentrated adding hexanes. Filtration of the cold mixture gave 17.4 g of (2,4-dichloro-pyrimidin-5-yl)-(2,3-difluoro-6-methoxy-phenyl)-methanone, MP 137–139° C.

Provenance & Evidence