反应详情

The product of the first step, 2-chloro-N-(2-formylphenyl)acetamide (0.869 g, 4.40 mmol) and ammonia, 7N solution in methanol (4.4 mL, 30.8 mmol) were stirred together at ambient in a sealed tube for 4.5 hours. A TLC (9:1 hexane EtOAc) check indicated that a new lower Rf spot had formed, however, plenty of starting material remained so stirring at ambient temperature was continued for another 19.5 hours, during which time a white precipitate had formed. Volatiles were removed under reduced pressure to give a beige solid that was treated with CHCl3. The portion that was soluble was checked by TLC (7:3 hexane/EtOAc). The major spot in the CHCl3-soluble portion was a new one with lower Rf than the starting material. The CHCl3 mixture was placed in the 0° C. freezer over the weekend. Insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on an Analogix IF-280 (Agilent SF10-4 g, 100% CHCl3). The product eluted in fractions #1-10. The product fractions were combined and concentrated under reduced pressure to give 2-(chloromethyl)quinazoline as a white solid (418 mg, 53.2%). 1H NMR (300 MHz, CDCL3) δ 9.45 (s, 1H), 8.09 8.04 (m, 1H), 7.99-7.92 (m, 2H), 7.70 (ddd, J=8.0, 6.9, 1.2 Hz, 1H), 4.92 (s, 2H).

1. customhad formed
2. customa white precipitate had formed
3. customVolatiles were removed under reduced pressure
4. customto give a beige solid
5. customwas placed in the 0° C. freezer over the weekend
6. customInsoluble material was removed by filtration
7. concentrationthe filtrate was concentrated under reduced pressure
8. customThe residue was purified by column chromatography on an Analogix IF-280 (Agilent SF10-4 g, 100% CHCl3)
9. washThe product eluted in fractions #1-10
10. concentrationconcentrated under reduced pressure