4-Amino-1-Boc-piperidine → 4-(5-Benzyloxy-pyridin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A stirred suspension of 5-benzyloxy-2-chloro-pyridine (12.4 g, 56.4 mmol, 1.0 equiv; prepared as described in WO 9728 128 A1 (Zeneca Ltd., UK)), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (11.31 g, 56.4 mmol, 1.0 equiv), palladium(II) acetate (0.51 g, 2.3 mmol, 0.04 equiv) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (1.44 g, 2.3 mmol, 0.04 equiv) in toluene (250 mL) was treated at rt with KOtert-Bu (6.71 g, 67.7 mmol, 1.2 equiv) and subsequently warmed to 70° C. After 7 h, the reaction mixture was poured into crashed ice and filtered over dicalite and extracted twice with toluene. The combined organic layers were dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 18.73 g (87%) of the title compound as a light yellow solid. MS (ISP): 384.1 [M+H]+.

Provenance & Evidence