2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → tert-butyl 2-(3-fluoro-4-((((1R,2R)-2-(1-(5-(methoxymethyl)pyrimidin-2-yl) piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)acetate

온도

60 °C

2-(4-((1R,2R)-2-(((4-bromo-2-fluorobenzyl)oxy)methyl)cyclopropyl)piperidin-1-yl)-5-(methoxymethyl)pyrimidine (Step B product, 1.0 g, 2.15 mmol) was dissolved in anhydrous THF (3 ml). The mixture was stirred for 5 min and TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (0.099 g, 0.108 mmol) and X-PHOS (0.103 g, 0.215 mmol) were added, followed by (2-(tert-butoxy)-2-oxoethyl)zinc(II) bromide (0.5 M solution in ether, 12.92 ml, 6.46 mmol). The mixture was heated at 60° C. overnight. The reaction mixture was quenched with aqueous NH4Cl, and the aqueous layer was extracted with EtOAc. The organic extracts were washed with brine, dried, and evaporated to give the crude product, which was purified by flash column (25 g SNAP, 5˜30% EtOAc in hexane) to afford 1.05 g (98%) of the desired product. Rf was 0.3 @ 20% EtOAc in hexanes (blue spot on CAM stain).

1. customThe reaction mixture was quenched with aqueous NH4Cl
2. extractionthe aqueous layer was extracted with EtOAc
3. washThe organic extracts were washed with brine
4. customdried
5. customevaporated
6. customto give the crude product, which
7. customwas purified by flash column (25 g SNAP, 5˜30% EtOAc in hexane)

ORD 기록

ord-0d4496a3c46c4cf99636cc5282518bc8

출처 데이터셋

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09006228B2