Sodium hydride → (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazinan-2-one

Participants

Reaction Steps

To a stirred suspension of sodium hydride (60% in oil; 5.6 mg; 0.139 mmol) in THF (0.5 mL) at 0° C. under an atmosphere of N2 was added a solution of (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazinan-2-one (Intermediate 22; 50 mg; 0.153 mmol) in THF (1 mL) dropwise. The resultant mixture stirred at 0° C. for 15 min prior to dropwise addition of 2-(bromomethyl)-1-iodo-4-trifluoromethyl)benzene (Intermediate 11; 50.7 mg; 0.139 mmol) as a solution in THF (0.5 mL). The reaction was allowed to warm to room temperature and stirred for 14 h. The reaction was quenched with H2O and partitioned between EtOAc (25 mL) and H2O (15 mL). The aqueous layer was re-extracted with EtOAc (3×25 mL) and the combined extracts were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient) to afford (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazinan-2-one as a clear oil. LCMS=611.7 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 8.02 (d, J=8.2 Hz, 1H), 7.91 (s, 2H), 7.89 (s, 1H), 7.52 (s, 1H), 7.29-7.26 (m, 1H), 5.44 (d, J=10.8 Hz, 1H), 4.88 (d, J=16.5 Hz, 1H), 4.62 (d, J=16.5 Hz, 1H), 3.77-3.70 (m, 1H), 2.45 (dd, J=14.1, 5.4 Hz, 1H), 2.06-1.98 (m, 1H), 1.22 (d, J=6.2 Hz, 3H).

Provenance & Evidence