Water → HCID 67972372, compound

HRID 1626298Notes

Reaction equation

HRID 1626298 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]2[CH2:20][CH:19]=[CH:18][CH2:17][C@@H:16]([NH:21][C:22]3[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)[C:15]2=[O:30])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-:32].[K+].[K+].CS(N)(=O)=O.C(O)(C)(C)C.[OH2:47].S(=O)(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[Cl:29][C:24]1[CH:23]=[C:22]([NH:21][C@@H:16]2[CH2:17][CH:18]([OH:47])[CH:19]([OH:32])[CH2:20][N:14]([C@@H:10]3[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]3)[C:15]2=[O:30])[CH:27]=[C:26]([F:28])[CH:25]=1

Participants

8

Reactant 6

HCID 962WaterHCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 72879MethanesulfonamideHCID 516919Sodium BisulfateHCID 67035111HCID 67035111, compound

Product 1

HCID 67972372HCID 67972372, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A degassed and purged argon stirring mixture of (R)-3-[(R)-3-(3-Chloro-5-fluoro-phenylamino)-2-oxo-2,3,4,7-tetrahydro-azepin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (250.0 mg, 0.5709 mmol), potassium carbonate (236.7 mg, 1.712 mmol), potassium ferricyanide(III) (563.8 mg, 1.712 mmol) and methanesulfonamide (109.4 mg, 1.150 mmol) in tert-butyl alcohol (3.003 mL, 31.40 mmol)/water (2.9905 mL, 166.00 mmol) in an ice bath was added potassium osmate, dihydrate (15.0 mg, 0.0407 mmol) The reaction mixture was allowed to reach room temperature and run for 48 h under argon atmosphere. The mixture was cooled in an ice bath and sodium bisulfate (178.21 mg, 1.7126 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 2 h. Ethyl acetate was added, the organic layer separated and the aqueous phase was extracted two more times with ethyl acetate. The combined organic phase were washed with 2 N KOH, dried over MgSO4 and concentrated under reduced pressure to afford 0.210 g, 78%. The crude diol was taken to the next step without purification. LCMS m/z 415.9 [M-tBu]+

Workup

  1. customA degassed
  2. custompurged
  3. customto reach room temperature
  4. temperatureThe mixture was cooled in an ice bath
  5. customthe organic layer separated
  6. extractionthe aqueous phase was extracted two more times with ethyl acetate
  7. washThe combined organic phase were washed with 2 N KOH
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customto afford 0.210 g, 78%
  11. customThe crude diol was taken to the next step without purification

Sources & evidence

ORD record
ord-e148242af23d493c9430172d8c53fbc2
Source dataset
uspto-grants-2014_07
Patent number
US08785440B2

Reaction notes

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