Tris(1,1-dimethylethyl)phosphine → Ethyl 1-benzyl-4-(4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)phenyl)piperidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a glovebox, ethyl 1-benzylpiperidine-4-carboxylate (2.0 g, 8.1 mmol), LiNCy2 (1.55 g, 8.3 mmol), and toluene (10 mL) were loaded sequentially into a 40 mL vial. In a separate vial, Pd(OAc)2 (22 mg, 0.1 mmol), P(t-Bu)3 (44 mg, 0.22 mmol), 1-bromo-4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)benzene (1.5 g, 4.1 mmol), and toluene (10 mL) were loaded sequentially and were then heated at 100° C. for 1 minute. The enolate solution in vial 1 was then added to the reaction mixture in vial 2 via a syringe. The combined mixture was heated at 100° C. for 40 minutes. The reaction mixture was cooled to 23° C. and passed through a short plug of silica gel eluting with EtOAc (20 mL). The filtrate was concentrated in vacuo and purified by silica gel chromatography (eluant: 5-20% EtOAc/hexane+2% TEA), affording 833 mg of ethyl 1-benzyl-4-(4-chloro-2-(3,3,3-triethoxyprop-1-ynyl)phenyl)piperidine-4-carboxylate.

Provenance & Evidence