Water → tert-Butyl [(6S,8S)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl]carbamate

HRID 2179458Notes

Reaction equation

HRID 2179458 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][NH:13][C:12](=[N:15][CH2:16][CH:17](O)[CH2:18][C:19]([F:22])([F:21])[F:20])[C@@H:11]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:10]1.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.C(=O)(O)[O-].[Na+].O>C(#N)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][N:13]2[C:17]([CH2:18][C:19]([F:22])([F:21])[F:20])=[CH:16][N:15]=[C:12]2[C@@H:11]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:10]1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 2724130Cornforth reagent3×HCID 178454084HCID 178454084, compound

Product 1

HCID 86698904tert-Butyl [(6S,8S)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl]carbamateYield 62.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of crude tert-butyl {(3S,5S)-5-(2,3-difluorophenyl)-2-[(4,4,4-trifluoro-2-hydroxybutyl)imino]piperidin-3-yl}carbamate (99.0 mg, 0.219 mmol) in acetonitrile (2.19 mL) was added pyridinium dichromate (247 mg, 0.657 mmol), and the mixture was stirred 2.5 h at 60° C. Pyridinium dichromate (392 mg, 1.04 mmol) was added and the resulting mixture stirred 72 h at 60° C. Pyridinium dichromate (300 mg, 0.797 mmol) was added and the resulting mixture stirred 4 h at 60° C. The mixture was cooled to ambient temperature and saturated aqueous sodium bicarbonate was added. Water was added, and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile→15% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (59 mg). MS 432.2 (M+1).

Workup

  1. stirringthe resulting mixture stirred 72 h at 60° C
  2. stirringthe resulting mixture stirred 4 h at 60° C
  3. temperatureThe mixture was cooled to ambient temperature
  4. extractionthe mixture was extracted with ethyl acetate (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile→15% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-890ecebcf9484340938d2bac4b0d0ae6
Source dataset
uspto-grants-2015_06
Patent number
US09067941B2

Reaction notes

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