Butyl vinyl ether → N-[(1R)-1-(4-Acetylphenyl)ethyl]methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

Charge a tube with N-[(1R)-1-(4-bromophenyl)ethyl]methanesulfonamide (29 g, 104 mmol), butyl vinyl ether (34.23 mL, 261 mmol), palladium(II) acetate (14.04 g, 63 mmol), bis-(1,3-diphenylphosphino)propane (52.7 g, 125 mmol) and potassium carbonate (17.3 g, 125 mmol). Degas the tube with nitrogen for 2 minutes, and then add H2O (69.5 mL) and DMF (69.5 mL). Seal the tube and stir at 110° C. for 20 h. Cool the reaction mixture to ambient temperature and add HCl (2N, 60 mL). Stir the mixture at ambient temperature for 10 min. Adjust the pH of the mixture to a pH of 7 using NaOH pellets; dilute with DCM (220 mL); filter through a Celite® pad; and sequentially wash the filtrate with aqueous K2CO3 (2×120 mL), brine (2×100 mL), and H2O (100 mL). Dry the mixture over MgSO4; filter; and concentrate the filtrate under reduced pressure to provide a residue. Purify the residue via flash column chromatography eluting with EtOAc in hexanes (step gradient of 0, 5, 10, 20, 30 and finally 40% EtOAc). Combine the product fractions and remove the solvents under reduced pressure to give the title compound (17.6 g, 70.0%) as a yellow oil. MS (m/z): 242 (M+1).

Provenance & Evidence