Triphenylphosphine → Methyl{2,6-difluoro-4-[2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethoxy]phenyl}acetate

To a stirred solution of methyl (2,6-difluoro-4-hydroxyphenyl)acetate (1.46 g, 7.22 mmol) in 10 ml anhydrous dichloromethane at RT was added a solution of 2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethanol (2.10 g, 7.22 mmol) in 20 ml anhydrous dichloromethane, followed by triphenylphosphine (polymer-bound, 3.79 g, 11.4 mmol), and di-tert-butyl azodicarboxylate (1.83 g, 7.94 mmol). The reaction mixture was stirred at RT for 3 hours. The mixture was filtered through Celite and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (Biotage column, 50 g) using a gradient eluent of 0-40% ethyl acetate in hexanes (900 ml) to afford the title compound. LC/MS (m/z) 476.4 (M+H)+.

1. filtrationThe mixture was filtered through Celite
2. concentrationconcentrated under reduced pressure
3. customThe residue was purified by column chromatography on silica gel (Biotage column, 50 g)

ORDレコード

ord-ef5f619f1acf4a1cb5b85813b9c4f7ae

出典データセット

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09018224B2