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

HRID 241303

Reaction equation

HRID 241303 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][OH:15])[CH2:9]1)C1C=CC=CC=1.C(N1CCCOCC1)C1C=CC=CC=1.[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33]>[C].[Pd].CO>[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33].[OH:15][CH2:14][C@@H:10]1[O:11][CH2:12][CH2:13][NH:8][CH2:9]1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 2776358(4-Benzylmorpholin-2-yl)methanol2×HCID 666627874-Benzyl-1,4-oxazepane2×

Product 1

HCID 66662997(R)-Morpholin-2-ylmethanol 2,2,2-trifluoroacetate saltYield 43%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

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.

Workup

  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.)

Sources & evidence

ORD record
ord-ebd89e6bdf2c49afaaf50375b94011a5
Source dataset
uspto-grants-2014_02
Patent number
US08648190B2

Linked notes

Loading…