反应详情

A flask containing 4-(4-aminobenzyl)morpholine from Preparation No. 22 (0.48 g) is treated with methanol (5 mL) and a few dozen dry molecular sieves (3 Å). The mixture is treated with acetic acid (1 mL) and terahydro-4H-pyran-4-one (0.24 mL). After 1 hour, the mixture is carefully treated with sodium cyanoborohydride (0.6 g) and heated to reflux under an argon atmosphere. After 1 hour, the mixture is cooled to room temperature and filtered with methanol washes. The filtrate is diluted with diethyl ether and washed with aqueous sodium hydroxide (2N). The aqueous is back-extracted with dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue is flash column chromatographed on silica eluting with 2% to 5% methanol in dichloromethane. The product-containing fractions are combined and evaporated to afford 0.34 g of N-[4-(4-morpholinylmethyl)phenyl]tetrahydro-2H-pyran-4-amine as a white solid.

1. customfrom Preparation No
2. customa few dozen dry molecular sieves (3 Å)
3. additionThe mixture is treated with acetic acid (1 mL) and terahydro-4H-pyran-4-one (0.24 mL)
4. additionthe mixture is carefully treated with sodium cyanoborohydride (0.6 g)
5. temperatureheated
6. temperatureto reflux under an argon atmosphere
7. waitAfter 1 hour
8. filtrationfiltered with methanol washes
9. additionThe filtrate is diluted with diethyl ether
10. washwashed with aqueous sodium hydroxide (2N)
11. extractionThe aqueous is back-extracted with dichloromethane
12. washThe combined organic layers are washed with brine
13. dry with materialdried over sodium sulfate
14. concentrationconcentrated under reduced pressure
15. customchromatographed on silica eluting with 2% to 5% methanol in dichloromethane
16. customevaporated