Potassium Carbonate → (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-(2-hydroxy-1,1-dimethylethyl)-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one

Participants

Reaction Steps

(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-trifluoromethyl)benzyl]-4-methyl-1,3-oxazinan-2-one (Intermediate 23; 30 mg; 0.049 mmol) was treated with 2-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methylpropan-1-ol (intermediate 26; 20 mg; 0.065 mmol), 1-1′-bis(di tert-butylphosphino)ferrocene palladium dichloride (3.2 mg; 0.0049 mmol), 1 N K2CO3 (1.2 mL) and THF (1.2 mL) as described in Example 38 to afford (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-(2-hydroxy-1,1-dimethylethyl)-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one as a clear glass. LCMS=664.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.86-7.80 (m, 2H), 7.76 (s, 1H), 7.67-7.61 (m, 2H), 7.41-7.37 (m, 2H), 7.21 (d, J=2.3 Hz, 1H), 6.96 (d, J=8.7 Hz, 1H), 5.38 (d, J=15.5 Hz, 1H), 4.95 (d, J=11 Hz, 1H), 4.09 (d, J=15.5 Hz, 1H), 3.81 (s, 3H), 3.65-3.63 (m, 1H), 3.58-3.55 (m, 1H), 3.41-3.35 (m, 1H), 2.25-2.20 (m, 1H), 1.80-1.72 (m, 1H), 1.28-1.25 (m, 6H), 1.07-1.03 (m, 3H).

Provenance & Evidence