Sodium Carbonate → (S)-6-(2-Hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-isopropyl-1H-pyrazol-4-yl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one

Participants

Reaction Conditions

Reaction Steps

2 M aqueous Na2CO3 solution (0.75 mL) was added to a solution of 4-bromo-1-isopropyl-1H-pyrazole (0.15 g) and (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-[(S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl]-1,3-oxazinan-2-one (0.25 g) in dimethylformamide (2 mL). The resulting mixture was sparged with argon for 10 min, before [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium(II) dichloromethane complex (13 mg) was added. The mixture was heated to 90° C. and stirred at this temperature for 6 h. Then another portion of [1,1′-bis(diphenyl-phosphino)-ferrocene]dichloro-palladium(II) dichloromethane complex (13 mg) was added and the mixture was further stirred at 100° C. overnight. After cooling to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated. The residue was purified by HPLC on reversed phase (acetonitrile/water) followed by chromatography on silica gel (tert-butyl methyl ether/dichloromethane/NH4OH 95:5:0.1) to afford the title compound as a solid. Yield: 23 mg (9% of theory); Mass spectrum (ESI+): m/z=462 [M+H]+.

Provenance & Evidence