Methanol → Tert-butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A sealable vial was charged with tert-butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(2-fluorophenyl)piperidine-1-carboxylate (0.138 g, 0.25 mmol) and 4-cyanophenylboronic acid (0.111 g, 0.75 mmol) in tetrahydrofuran (2 mL) at 0° C. To the reaction solution was added 1N potassium hydroxide (0.88 mL, 0.88 mmol) and Tetrakis(triphenylphosphine)palladium(0) (0.058 g, 0.05 mmol). The vial was purged with nitrogen and sealed. The sealed vial was heated in a microwave reactor at 120° C. for 2 hr. The reaction was cooled to room temperature and diluted with 4 mL ethyl acetate. The organic layer was separated, dried over Na2SO4 and evaporated in vacuo. The crude oil was purified by silica gel chromatography (5% ethyl acetate/95% hexanes→35% ethyl acetate/65% hexanes) to afford 0.123 g (87%) of the desired ether. Mass spec.: 591.22 (MNa)+; LC tr=4.318 min. (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=4 min, Flow rate=4 mL/min).

Provenance & Evidence