Methyl morpholine oxide → 5-acetyl-2-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-benzaldehyde

HRID 577812Notes

Reaction equation

HRID 577812 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[C:14]([CH2:15][OH:16])=[CH:13][C:12]([C:17](=[O:19])[CH3:18])=[C:11]([F:20])[C:10]=2[F:21])[CH2:3]1.C[N+]1([O-])CCOCC1>C(Cl)Cl.CC#N.CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O>[C:17]([C:12]1[C:11]([F:20])=[C:10]([F:21])[C:9]([N:4]2[CH2:3][C@H:2]([CH3:1])[O:7][C@H:6]([CH3:8])[CH2:5]2)=[C:14]([CH:13]=1)[CH:15]=[O:16])(=[O:19])[CH3:18]

Participants

5

Reactant 2

HCID 82029Methyl morpholine oxideHCID 866580491-[4-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-2,3-difluoro-5-hydroxymethyl-phenyl]-ethanone2×

Product 1

HCID 588470585-acetyl-2-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-benzaldehyde

Reagents, catalysts & solvents 2

HCID 178419074HCID 178419074, compoundCatalystHCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

To an ice-cooled solution of 1-[4-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-2,3-difluoro-5-hydroxymethyl-phenyl]-ethanone (Intermediate 10, 3.2 g, 9.72 mmol) in CH2Cl2/CH3CN mixture (20 mL, 1:1 v/v) was added NMO (2.2 g, 19.44 mmol) followed by TPAP (340 mg, 0.97 mmol) and mixture stirred for 2 hours at room temperature. The reaction mixture filtered thorough silica gel bed and washed with EtOAc. The organic phase concentrated under reduced pressure to give the title compound as a yellow crystalline solid. Yield: 3.0 g (94%).

Workup

  1. filtrationThe reaction mixture filtered thorough silica gel bed
  2. washwashed with EtOAc
  3. concentrationThe organic phase concentrated under reduced pressure

Sources & evidence

ORD record
ord-c8ff7012e925423eb086360be4cf0fcd
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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