Water → tert-Butyl[(5R,6S,8S)-5-methyl-6-phenyl-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-8-yl]carbamate

HRID 2179467Notes

Reaction equation

HRID 2179467 reaction equation
[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH3:20])[NH:10][C:9]1=[N:21][CH2:22][CH:23](O)[CH2:24][C:25]([F:28])([F:27])[F:26])([CH3:4])([CH3:3])[CH3:2].[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>[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH3:20])[N:10]2[C:23]([CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:22][N:21]=[C:9]12)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 2724130Cornforth reagent2×HCID 137231131tert-Butyl{(3S,5S,6R)-6-methyl-5-phenyl-2-[(4,4,4-trifluoro-2-hydroxybutyl)imino]piperidine-3-yl}carbamate

Product 1

HCID 131733072tert-Butyl[(5R,6S,8S)-5-methyl-6-phenyl-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-8-yl]carbamateYield 20.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl{(3S,5S,6R)-6-methyl-5-phenyl-2-[(4,4,4-trifluoro-2-hydroxybutyl)imino]piperidine-3-yl}carbamate (100 mg, 0.23 mmol) in acetonitrile (4.7 mL) was added pyridinium dichromate (440 mg, 1.17 mmol), and the mixture was stirred 45 min at 70° C. Pyridinium dichromate (440 mg, 1.17 mmol) was added, and the mixture was stirred 30 min at 70° 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→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (19.6 mg). MS 410.3 (M+1)

Workup

  1. stirringthe mixture was stirred 30 min at 70° C
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionthe mixture was extracted with ethyl acetate (3×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-8d94a86ebe8a42b6be0d2b3ce5d956b1
Source dataset
uspto-grants-2015_06
Patent number
US09067941B2

Reaction notes

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