反应详情

A 1M solution of zinc chloride in ether (12.8 mL, 12.8 mmol) was added to a solution of 2,6-dichloro-5-trifluoromethylpyrimidine (2.76 gm, 12.8 mmol) in 20 mL of dichloroethane and t-butanol (1:1) under an atmosphere of nitrogen. The reaction mixture was stirred at rt for 30 min, cooled to 0° C. and then treated with a solution of (4-amino-3-methyl benzyl)phosphonic acid diethyl ester (Compound 33D, 2.2 gm, 8.5 mmol) in dichloroethane and t-butanol (10 mL, 1:1) slowly over 10 min through an addition funnel. After 1 hour, diisopropylethylamine (2.2 mL, 12.6 mmol) was added and then reaction gradually warmed up to rt over 4 hrs. The reaction mixture was refrigerated overnight causing the desired product to precipitate out of solution. This was collected by filtration to afford 2.7 g of the title compound (73%). 1H NMR (300 MHz, CDCl3): δ 1.21-1.26 (m, 6H), 2.3 (s, 3H), 3.15 (d, J=22.0 Hz, 2H), 3.99-4.09 (m, 4H), 7.17 (m, 3H), 7.72 (d, J=7.5 Hz, 1H), 8.52 (s, 1H).

1. temperaturecooled to 0° C.
2. waitAfter 1 hour
3. customreaction
4. temperaturegradually warmed up to rt over 4 hrs
5. waitThe reaction mixture was refrigerated overnight