Ammonia → (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine

HRID 331136Notes

Reaction equation

HRID 331136 reaction equation
[F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5](=S)[NH:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12].[NH3:27].C(OO)(C)(C)C>CO>[F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5]([NH2:27])=[N:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 6410tert-Butyl hydroperoxideHCID 86671875(R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione

Product 1

HCID 66558529(R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amineYield 41%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione (239 mg, 627 μmol) in methanol (7.2 ml), was treated with ammonia (7 M in methanol, 5.37 ml) and tert-butyl hydroperoxide (70% in water, 517 μl). The mixture was stirred at room temperature for 16 hours. For the workup, the reaction mixture was extracted with water and dichloromethane. The organic layer was washed with water and brine, the aqueous layers were reextracted with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated to give brown oil. The residue was purified by chromatography on an amino-silica phase using dichloromethane as the eluent. The (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (94 mg, 41% yield) was obtained as a white foam. MS (ISP): m/z=365.2 [M+H]+.

Workup

  1. extractionFor the workup, the reaction mixture was extracted with water and dichloromethane
  2. washThe organic layer was washed with water and brine
  3. dry with materialThe combined organic layers were dried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customto give brown oil
  7. customThe residue was purified by chromatography on an amino-silica phase

Sources & evidence

ORD record
ord-c075765f41e949b39b2acb42cc108357
Source dataset
uspto-grants-2014_11
Patent number
US08877744B2

Reaction notes

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