4-Benzyl-2-methyl-6-(trifluoromethyl)morpholin-3-one → 4-Benzyl-cis-2-methyl-6-(trifluoromethyl)morpholine

HRID 1820652Notes

Reaction equation

HRID 1820652 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([N:14]1[CH2:19][CH:18]([C:20]([F:23])([F:22])[F:21])[O:17][CH:16]([CH3:24])[C:15]1=O)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH2:7]([N:14]1[CH2:19][C@H:18]([C:20]([F:23])([F:21])[F:22])[O:17][C@H:16]([CH3:24])[CH2:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

3

Reactant 2

HCID 184555914-Benzyl-2-methyl-6-(trifluoromethyl)morpholin-3-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 588470294-Benzyl-cis-2-methyl-6-(trifluoromethyl)morpholine

Conditions

Temperature
60 °C

Procedure

Dry LiAlH4 (797 mg, 21 mmol, Aldrich) is suspended in dry, inhibitor free THF (15 ml) and treated with a solution of 4-benzyl-2-methyl-6-(trifluoromethyl)morpholin-3-one (2.73 g, 10 mmol) in dry, inhibitor free THF (15 ml). The mixture is heated to 60° C. with stirring for 30 minutes. The mixture is diluted with MTBE (25 mL) and quenched sequentially with H2O (0.8 mL), 6.0 M NaOH (0.8 mL) and H2O (2.4 mL). The white slurry is filtered and the inorganic salts were washed with MTBE (200 mL). The solvent is removed by rotary evaporation and the product is purified in 3 portions on Biotage Flash 40M+ cartridges using a 10 minute linear gradient of 3% -10% MTBE in heptane. The products are combined and dried under high vacuum yielding a colorless oil.

Workup

  1. customin dry
  2. customin dry
  3. additionThe mixture is diluted with MTBE (25 mL)
  4. customquenched sequentially with H2O (0.8 mL), 6.0 M NaOH (0.8 mL) and H2O (2.4 mL)
  5. filtrationThe white slurry is filtered
  6. washthe inorganic salts were washed with MTBE (200 mL)
  7. customThe solvent is removed by rotary evaporation
  8. customthe product is purified in 3 portions on Biotage Flash 40M+ cartridges
  9. waitusing a 10 minute linear gradient of 3% -10% MTBE in heptane
  10. customdried under high vacuum
  11. customyielding a colorless oil

Sources & evidence

ORD record
ord-d5f38d0dbb4f47dbb75b6e50fe5cac6d
Source dataset
uspto-grants-2009_10
Patent number
US07605157B2

Reaction notes

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