反应详情

A stirred solution of nitrile 141 (5.78 g, 16.6 mmol) in dry DMF (50 mL) was treated at 0° C. with NaH (0.80 g, 20.0 mmol, 60% in oil). The resulting suspension was warmed to room temperature for 30 min, then cooled to 0° C. again and treated with 1,3-dichloropropene (4.8 mL, 52 mmol, mixed isomers). After stirring at room temperature for a further 6 h, the mixture was diluted with water and extracted with EtOAc (×3). The combined organic extracts were washed with water (×3), dried, and concentrated to dryness under high vacuum at 80° C. The residue was chromatographed on silica gel, eluting with CH2Cl2, to give tert-butyl 1-bromo-6-cyano-2-naphthyl(3-chloro-2-propenyl)carbamate (142) (6.77 g, 96%) as a foam; 1H NMR [(CD3)2SO] (mixture of rotamers and E and Z forms) δ 8.69 (s, 1H), 8.35 (d, J=8.8 Hz, 1H), 8.13, 8.12 (2 d, J=8.6 Hz, 1H), 7.96 (d, J=8.9 Hz, 1H), 7.69, 7.63 (2d, J=8.7 Hz, 1H), 6.42-6.29 (m, 1H), 6.17-5.99 (m, 1H), 4.55-4.45, 4.40-4.19, 4.15-3.98 (3 m, 2H), 1.48, 1.24 (2 s, 9H). HRMS (FAB) calcd. for C19H1979Br35ClN2O2(m/z 421.0318, found 421.0306.

1. temperaturecooled to 0° C. again
2. extractionextracted with EtOAc (×3)
3. washThe combined organic extracts were washed with water (×3)
4. customdried
5. concentrationconcentrated to dryness under high vacuum at 80° C
6. customThe residue was chromatographed on silica gel
7. washeluting with CH2Cl2