(R)-5-(5-(3,6-dihydro-2H-pyran-4-yl)-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one → (R)-6,6-difluoro-5-(2-fluoro-5-(tetrahydro-2H-pyran-4-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepan-3-one

HRID 331144Notes

Reaction equation

HRID 331144 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:8]=[CH:9][C:10]([F:26])=[C:11]([C@:13]3([CH3:25])[C:19]([F:21])([F:20])[C:18]([CH3:23])([CH3:22])[O:17][CH2:16][C:15](=[O:24])[NH:14]3)[CH:12]=2)[CH2:3][CH2:2]1>C(OCC)(=O)C.[Pd]>[F:21][C:19]1([F:20])[C:18]([CH3:22])([CH3:23])[O:17][CH2:16][C:15](=[O:24])[NH:14][C@@:13]1([C:11]1[CH:12]=[C:7]([CH:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)[CH:8]=[CH:9][C:10]=1[F:26])[CH3:25]

Participants

4

Reactant 1

HCID 68380032(R)-5-(5-(3,6-dihydro-2H-pyran-4-yl)-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one

Product 1

HCID 68380531(R)-6,6-difluoro-5-(2-fluoro-5-(tetrahydro-2H-pyran-4-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepan-3-oneYield 95%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (R)-5-(5-(3,6-dihydro-2H-pyran-4-yl)-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one [Example 5a)] (256 mg, 693 μmol) in ethyl acetate (20 ml) was hydrogenated at room temperature for 16 hours using palladium on carbon (10%: 74 mg, 69.3 μmol) as the catalyst. The reaction mixture was filtered and evaporated to give the crude (R)-6,6-difluoro-5-(2-fluoro-5-(tetrahydro-2H-pyran-4-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepan-3-one (244 mg, 95% yield) as a colorless oil. MS (ISP): m/z=372.2 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customevaporated

Sources & evidence

ORD record
ord-4eeb849cff3d4662bfe4294507dc2c64
Source dataset
uspto-grants-2014_11
Patent number
US08877744B2

Reaction notes

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