(Pyrimidin-5-yl)boronic acid → (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepan-3-one

Participants

Reaction Steps

In analogy to the procedure described in Example 1 (method A), the reaction of (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one (intermediate B6.1) (311 mg, 849 μmol) and pyrimidin-5-boronic acid (116 mg, 934 μmol) in tetrahydrofuran (8 ml) and water (4 ml) with [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) dichloromethane complex (34.7 mg, 42.5 μmol) as the catalyst yielded, after chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 10:90 as the eluent, the (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepan-3-one (263 mg, 85% yield) as a white foam. MS (ISP): m/z=366.1 [M+H]+.

Provenance & Evidence