反应详情

16 g of powdered molecular sieve 3 Å and 52.7 ml of ethyl 2-chloroacetoacetate (380.8 mmol; 5 equivalents) were added to 24 g of 5-bromo-3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine (Example 17A; 76.2 mmol; 1 equivalent) in 400 ml of ethanol, and the mixture was heated at reflux overnight. A further 8 g of molecular sieve were added, and the mixture was heated at reflux for a further 24 h. The reaction mixture was concentrated under reduced pressure and the residue was taken up in dichloromethane and chromatographed on silica gel (dichloromethane/methanol 20:1 as mobile phase). The product-containing fractions were concentrated and the residue was stirred with 100 ml of diethyl ether for 30 min. The product was then filtered off, washed with a little diethyl ether and dried. This gave 15 g (45% of theory) of the title compound.

1. temperaturethe mixture was heated
2. temperatureat reflux overnight
3. additionA further 8 g of molecular sieve were added
4. temperaturethe mixture was heated
5. temperatureat reflux for a further 24 h
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. customchromatographed on silica gel (dichloromethane/methanol 20:1 as mobile phase)
8. concentrationThe product-containing fractions were concentrated
9. filtrationThe product was then filtered off
10. washwashed with a little diethyl ether
11. customdried