反应详情

温度

55 °C

A solution of 1,1-dimethylethyl (1-{2-[3-fluoro-6-(methyloxy)-1,5-naphthyridin-4-yl]-3-hydroxypropyl}-4-piperidinyl)carbamate (18.28 g, containing some non-alcohol impurity and a little MeOH, judged to contain 40 mmol alcohol-containing compounds) in dichloromethane (180 ml) was stirred under argon, ice-cooled and treated with triethylamine (11.1 ml, 80 mmol) and methanesulfonic anhydride (8.7 g, 50 mmol). After 1 hour the solution was heated to reflux for 2 days, evaporated and redissolved in chloroform (180 ml). This solution was heated under argon at 55° C. for 3 days, cooled, washed with aqueous sodium bicarbonate and the aqueous twice re-extracted with chloroform. The combined organic phases were dried and evaporated. Chromatography of the residue (methanol/dichloromethane gradient) and rechromatography of some impure fractions gave the product (13.35 g, containing 12.5% dichloromethane by weight).

1. temperatureice-cooled
2. temperatureAfter 1 hour the solution was heated
3. temperatureto reflux for 2 days
4. customevaporated
5. dissolutionredissolved in chloroform (180 ml)
6. temperaturecooled
7. washwashed with aqueous sodium bicarbonate
8. extractionthe aqueous twice re-extracted with chloroform
9. customThe combined organic phases were dried
10. customevaporated
11. customChromatography of the residue (methanol/dichloromethane gradient) and rechromatography of some impure fractions gave