Trifluoroacetic acid → (R)-Morpholin-2-ylmethanol 2,2,2-trifluoroacetate salt

Temperatur

20 °C

In the same manner as in Example 3, a mixture containing N-benzyl-2-hydroxymethylmorpholine, N-benzyl-1,4-oxazepane and other byproducts (121.1 g, N-benzyl-2-hydroxymethylmorpholine:N-benzyl-1,4-oxazepane compound=75.1:24.9). To this mixture were added methanol (200 ml), trifluoroacetic acid (61.8 g, 0.540 mol), and palladium carbon (11.0 g when dry), and the mixture was reacted under a hydrogen stream at 25° C. for 15 hr. Palladium carbon was filtered off, and methanol was evaporated under reduced pressure. The residue was subjected twice to azeotropic distillation with dehydrating with 2-propanol (100 ml). To the residue after azeotropic distillation with dehydrating was added ethyl acetate (450 ml) at 40° C., and the mixture was cooled to 20° C. Seed crystal was added and, after crystallization, the mixture was cooled to 0° C. and stirred for 1 hr. The crystals were collected by filtration, washed withed twice with ethyl acetate (100 ml) and dried (1 mmHg, 40° C.) to give (R)-2-hydroxymethylmorpholine trifluoroacetate (53.7 g) (yield from (S)-epichlorohydrin: 43.0%). The obtained (R)-2-hydroxymethylmorpholine trifluoroacetate was analyzed by HPLC to find an optical purity of 99% ee.

1. customthe mixture was reacted under a hydrogen stream at 25° C. for 15 hr
2. filtrationPalladium carbon was filtered off
3. custommethanol was evaporated under reduced pressure
4. distillationThe residue was subjected twice to azeotropic distillation
5. distillationTo the residue after azeotropic distillation with dehydrating
6. additionwas added ethyl acetate (450 ml) at 40° C.
7. additionSeed crystal was added
8. customafter crystallization
9. temperaturethe mixture was cooled to 0° C.
10. filtrationThe crystals were collected by filtration
11. washwashed
12. customdried (1 mmHg, 40° C.)

ORD-Eintrag

ord-ebd89e6bdf2c49afaaf50375b94011a5

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08648190B2