反应详情

Pyrimidine-5-carbonitrile (5 g, 47.6 mmol, 1 eq) was taken in a dry THF under an argon atmosphere. Titanium isopropoxide (17 ml, 57.1 mmol, 1.2 eq) was then added slowly at ambient temperature and the resulting mixture was stirred for 15 mins. To the above stirred mixture was slowly added ethyl magnesium bromide (107 ml, 2.2 eq, 1 M in THF) via syringe at ambient temperature (during the addition of EtMgBr, the reaction mixture turned black). The reaction mass was stirred for an hour, and BF3.EtO (16.7 ml, 135 mmol, 2.8 eq) was then added slowly through syringe to the mixture at 0° C. The reaction was then allowed to warm to ambient temperature and the stirring was continued for another one hour. Finally the reaction was quenched by adding 50 ml of water, and the reaction mixture was passed through Celite and the bed washed with water and ethyl acetate. The filtrate was basified with 10% NaOH solution (pH=9) and then extracted with DCM and washed with brine. The required product was purified by silica gel (60-120) column chromatography using 4% methanol/DCM as the eluent. Yield: 0.1 g (5%) 1H NMR (400 MHz, DMSO-d6): δ1.04-1.08 (m, 2H), 1.18-1.25 (m, 2H), 8.26 (d, 2H), 9.05 (s, 1H). LCMS: (ES+) m/z=136 (M+H)+

1. customat ambient temperature
2. stirringThe reaction mass was stirred for an hour
3. additionEtO (16.7 ml, 135 mmol, 2.8 eq) was then added slowly through syringe to the mixture at 0° C
4. waitthe stirring was continued for another one hour
5. customFinally the reaction was quenched
6. additionby adding 50 ml of water
7. washthe bed washed with water and ethyl acetate
8. extractionextracted with DCM
9. washwashed with brine
10. customThe required product was purified by silica gel (60-120) column chromatography