Sodium hydride → (2R,6R)-4-Benzyl-2-methyl-6-(trifluoromethyl)morpholin-3-one

HRID 922773Notes

Reaction equation

HRID 922773 reaction equation
[CH2:1]([N:8]([CH2:14][C@@H:15]([OH:20])[C:16]([F:19])([F:18])[F:17])[C:9](=[O:13])[C@@H:10](O)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>C1COCC1>[CH2:1]([N:8]1[CH2:14][C@H:15]([C:16]([F:17])([F:18])[F:19])[O:20][C@H:10]([CH3:11])[C:9]1=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 89544014(S)-N-Benzyl-2-hydroxy-N-((R)-3,3,3-trifluoro-2-hydroxypropyl)propanamide

Product 1

HCID 89543806(2R,6R)-4-Benzyl-2-methyl-6-(trifluoromethyl)morpholin-3-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S)—N-benzyl-2-hydroxy-N—((R)-3,3,3-trifluoro-2-hydroxypropyl)propanamide (4-3) in THF (200 ml) was cooled to 0° C. To this was added NaH (60% dispersion in mineral oil, 1.05 g, 26.3 mmol) portionwise as a solid. After 1 hr the cooling bath was removed and the mixture allowed to warm to rt. After an additional hour the mixture was quenched with brine. The mixture was diluted with H2O and extracted with EtOAc (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated to afford (2R,6R)-4-benzyl-2-methyl-6-(trifluoromethyl)morpholin-3-one (4-4) as a clear oil which was sufficiently pure for use in the next step.

Workup

  1. customAfter 1 hr the cooling bath was removed
  2. customAfter an additional hour the mixture was quenched with brine
  3. additionThe mixture was diluted with H2O
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0db064b46ace42c1a6473ac23dcba1da
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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