Dichloromethane → (3S,5S)-3,5-Dimethylmorpholine--hydrogen chloride (1/1)

A mixture of (3S)-3,5-dimethylmorpholine hydrochloride (8.3 g), di-tert-butyl dicarbonate (14.34 g) and sodium hydroxide (5.48 g) in water (30 ml) were stirred at room temperature overnight. Water (50 ml) and isopropyl ether were added to the mixture and the organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of ethyl acetate and n-hexane (1:9) as an eluent to give (3S,5S)-4-tert-butoxycarbonyl-3,5-dimethylmorpholine (3.55 g) and meso-4-tert-butoxycarbonyl-3,5-dimethylmorpholine (2.84 g) (the former was less polar). (3S,5S)-4-tert-butoxycarbonyl-3,5-dimethylmorpholine (3.55 g) was dissolved in a mixture of dichloromethane (20 ml) and trifluoroacetic acid (20 ml) and the mixture was stirred at room temperature for 2 hours. After removal of the solvent under reduced pressure, 1N sodium hydroxide solution (20 ml) and dichoromethane were added thereto. The organic phase was separated, dried over magnesium sulfate, and was added 4N hydrogen chloride in ethyl acetate (20 ml). The mixture was evaporated in vacuo and the residue was triturated with a mixture of dichloromethane and isopropyl ether to give (3S,5S)-3,5-dimethylmorpholine hydrochloride (1.56 g) as a white solid.

1. customAfter removal of the solvent under reduced pressure, 1N sodium hydroxide solution (20 ml) and dichoromethane
2. additionwere added
3. customThe organic phase was separated
4. dry with materialdried over magnesium sulfate
5. additionwas added 4N hydrogen chloride in ethyl acetate (20 ml)
6. customThe mixture was evaporated in vacuo
7. customthe residue was triturated with a mixture of dichloromethane and isopropyl ether

ORD record

ord-23307795ccf64a48a7e84f7a9885073c

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06924278B2