2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → Tert-butyl 2-(2,6-difluoro-4-(2-((1S,2R)-2-(1-(5-methoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethoxy)phenyl)acetate

Participants

Reaction Conditions

Reaction Steps

To 2-(4-((1R,2S)-2-(2-(4-bromo-3,5-difluorophenoxy)ethyl)cyclopropyl)piperidin-1-yl)-5-methoxypyrimidine (1.86 g, 3.97 mmol) in THF (5 ml) was added tris(dibenzylideneacetone)dipalladium(0) (0.364 g, 0.397 mmol) and X-PHOS (0.379 g, 0.794 mmol), followed by (2-tert-butoxy-2-oxoethyl)zinc(II) bromide (0.5 M in ethyl ether, 23.83 ml, 11.91 mmol). The mixture was degassed under N2 for 10 min then heated at 60° C. overnight. The mixture was diluted with sat. NH4Cl (50 ml), and the aqueous phase extracted with EtOAc (50 ml×2). The organic fractions were combined, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (50 g SNAP, 5˜30% EtOAc in hexane) to afford the titled compound. LC/MS (m/z): 504 (M+H)+. Rf was 0.28 @ 25% EtOAc in hexanes (blue spot on CAM stain)

Provenance & Evidence