Sodium hydride → (6S)-3-{[2'-chloro-5'-isopropyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-6-(2-methoxyphenyl)-1,3-oxazinan-2-one

Participants

Reaction Steps

(6S)-6-(2-methoxyphenyl) 1,3-oxazinan-2-one (prepared from ethyl-4-(2-methoxyphenyl)-4-oxobutyrate by a procedure analogous to that reported for Intermediate 21; 20 mg; 0.10 mmol) was treated with sodium hydride (60% in oil; 8.0 mg; 0.20 mmol) and 2-(bromomethyl)-2′-chloro-5′-isopropyl-4-(trifluoromethyl)-biphenyl (Intermediate 27; 39 mg; 0.10 mmol) as described in Example 11 to afford (6S)-3-{[2′-chloro-5′-isopropyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-6-(2-methoxyphenyl)-1,3-oxazinan-2-one as a white solid. LCMS=518.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.76 (s, 1H), 7.64 (d, J=8.1 Hz, 1H), 7.50 (d, J=6.4 Hz, 1H), 7.44 (s, 1H), 7.37-7.35 (m, 1H), 7.34-30 (m, 1H), 7.26-7.24 (m, 1H), 7.09 (dd, J=7.8, 2.3 Hz, 1H), 7.06-7-7.00 (m, 1H), 6.90 (d, J=8.2 Hz, 1H), 5.66 (dd, J=8.7, 3.0 Hz, 1H), 4.71 (d, J=15.8 Hz, 1H), 4.39 (d, J=15.8 Hz, 1H), 3.85 (s, 3H), 3.25-3.17 (m, 1H), 3.09-3.04 (m, 1H), 2.97-2.92 (m, 1H), 2.31-2.25 (m, 1H), 2.06-1.99 (m, 1H) 1.28 (d, J=7.1 Hz, 6H).

Provenance & Evidence