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

温度

60 °C

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)

1. customThe mixture was degassed under N2 for 10 min
2. additionThe mixture was diluted with sat. NH4Cl (50 ml)
3. extractionthe aqueous phase extracted with EtOAc (50 ml×2)
4. washwashed with brine
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (50 g SNAP, 5˜30% EtOAc in hexane)

ORDレコード

ord-498412829ae744608e75a5f689840298

出典データセット

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09018224B2