反应详情

温度

-78 °C

A solution of 5-(2-pyridyl)oxazole (Saikachi, H.; Kitagawa, T.; et al. Chem. Pharm. Bull. 1969, 27, 793-796) (600 mg, 4.11 mmol) in anhydrous THF (15 mL) at −78° C. was treated dropwise with a solution of n-BuLi (2.2 M in hexanes, 2.4 mL, 4.52 mmol,) under N2 and the resulting solution was stirred at −78° C. for 20 min. A solution of ZnCl2 (0.5 M in THF, 18 mL, 8.22 mmol,) was added, and the mixture was warmed to 0° C. After stirring at 0° C. for 45 min, CuI (850 mg, 4.46 mmol) was added to the mixture. After the mixture was stirred at 0° C. for 10 min, a solution of 7-(trimethylsilyl)hept-6-ynoyl chloride (1.2 equiv; prepared from 7-(trimethylsilyl)hept-6-ynoic acid and oxalyl chloride) in anhydrous THF (9 mL) was added dropwise, and the mixture was stirred at 0° C. for an additional 1 h. The reaction mixture was diluted with a 1:1 mixture of hexanes and EtOAc (60 mL) and washed with 15% aqueous NH4OH (2×30 mL), water (30 mL) and saturated aqueous NaCl (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated. Column chromatography (SiO2, 4×6 cm, 30% EtOAc-hexanes) afforded 1-oxo-1-[5-(2-pyridyl)oxazol-2-yl]-7-(trimethylsilyl)hept-6-yne (3a, 875 mg, 2.68 mmol, 74%) as a tan oil: 1H NMR (CDCl3, 400 MHz) 8.68 (m, 1H), 7.89-7.86 (m, 2H), 7.82 (td, 1H, J=7.6, 1.8 Hz), 7.34-7.31 (m, 1H), 3.15 (t, 2H, J=7.3 Hz), 2.30 (t, 2H, J=7.2 Hz), 1.94-1.86 (m, 2H), 1.68-1.60 (m, 2H), 0.14 (s, 3H); 13C NMR (CDCl3, 100 MHz) 187.9, 157.2, 153.2, 150.0, 146.1, 137.0, 126.8, 124.1, 120.3, 106.6, 84.8, 38.4, 27.9, 22.9, 19.6, 0.0; IR (film) νmax 2955, 2867, 2173, 1699, 1603, 1576, 1504, 1469, 1426, 1383, 1249, 1152, 1118, 1083, 1024, 929, 842, 784, 760 cm−1; ESI-TOF m/z 327.1530 (C18H22N2O2Si+H+ requires 327.1523).

1. temperaturethe mixture was warmed to 0° C
2. stirringAfter stirring at 0° C. for 45 min
3. stirringAfter the mixture was stirred at 0° C. for 10 min
4. stirringthe mixture was stirred at 0° C. for an additional 1 h
5. washwashed with 15% aqueous NH4OH (2×30 mL), water (30 mL) and saturated aqueous NaCl (30 mL)
6. dry with materialThe organic layer was dried over anhydrous Na2SO4
7. filtrationfiltered
8. customevaporated