Reaction Steps
4-[4,4-dimethyl-2-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-6-yl]thiophene-2-carbonitrile (0.25 g, 0.74 mmol) was dissolved in DMF (10 mL), NaH (0.09 g, 2.22 mmol) was added and the mixture was stirred for 30 minutes prior to the addition of acetyl chloride (0.079 mL, 1.11 mmol). Upon disappearance of the starting material the reaction mixture was poured into brine (100 mL) and the product extracted with ether (150 mL), dried over sodium sulfate and concentrated. The residue was purified by a flash column chromatography (silica gel, 25% ethyl acetate/hexane) to yield 4-[1-acetyl-4,4-dimethyl-2-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-6-yl]thiophene-2-carbonitrile (0.1 g, 36%) as an amorphous solid: 1H-NMR (DMSO-d6) δ 8.58 (s, 1H), 8.5 (s, 1H), 7.83-7.80 (m, 2H), 7.64 (d, 1H, J=8.74 Hz), 6.42 (q, 1H, J=10 Hz), 2.24 (s, 3H), 1.73 (s, 3H), 1.42 (s, 3H). EXAMPLE 35 (6(5-Cyanothien-3-yl)-4,4-dimethyl-2(tnfluoromethyl)-2H-3,1-benzoxazin-1(4H)-yl)methyl Pivalate 4-[4,4-dimethyl-2-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-6-yl]thiophene-2-carbonitrile (0.30 g, 0.89 mmol) was dissolved in DMF (10 mL), NaH (0.065 g, 2.7 mmol) was added and the was mixture stirred for 30 minutes prior to the addition of tert-butyl chloroacetate (0.19 mL, 1.3 mmol). Upon disappearance of the starting material the reaction mixture was poured into brine (100 mL) and the product extracted with ether (150 mL), dried over sodium sulfate and concentrated. Flash column chromatography (silica gel, 8% ethyl acetate/hexane) gave (6(5-cyanothien-3-yl)-4,4-dimethyl-2-(trifluoromethyl)-2H-3,1-benzoxazin-1 (4H)-yl)methyl pivalate (0.127 g, 32%) as an amorphous solid: 1H-NMR (CDCl3) δ 7.82 (s, 1H), 7.58 (s, 1H), 7.41 (dd, 1H, J=8.33, 1.98 Hz), 7.25 (d, 1H, J=1.98 Hz) 7.10 (d, 1H, J=8.33 Hz), 6.79 (d, 1H, J=8.33 Hz), 5.66 (d, 1H, J=11.9 Hz), 5.38 (d, 1H, J=11.9 Hz), 1.72 (s, 3H), 1.55 (s, 3H), 1.18 (s, 9H).
