Di-tert-butyl azodicarboxylate → 1-methylcyclopropyl 4-[(1R,2S)-2-{2-[3-fluoro-4-(2-methoxy-2-oxoethyl)phenoxy]ethyl}cyclopropyl]piperidine-1-carboxylate

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Reaction Steps

To a solution of 1-methylcyclopropyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidine-1-carboxylate (Intermediate 9, 0.484 g, 1.81 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of methyl (2-fluoro-4-hydroxyphenyl)acetate (0.400 g, 2.17 mmol) in 10 ml anhydrous dichloromethane, triphenylphosphine, polymer-bound (1.42 g, 4.10 mmol), and di-tert-butyl azodicarboxylate (0.834 g, 3.61 mmol). The reaction mixture was stirred at RT for 3 hours. It was filtered by Celite and concentrated. The residue was purified on Biotage column (50 g silica gel) using a gradient eluent of 0-50% ethyl acetate in hexanes (1000 ml) to afford the title compound. LC/MS (m/z) 434.2 (M+H)+.

Provenance & Evidence