Ethanol → HCID 136348244, compound

HRID 1691769Notes

Reaction equation

HRID 1691769 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([F:9])[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([CH2:16][N:17]([C@@H:25]([C:27]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH:30]=[CH:29][CH:28]=3)[CH3:26])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:12]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:11]2)=[C:5]([F:43])[CH:4]=1)#[N:2].Cl.[NH2:45]O.C(O)C.Cl[C:51]([O:53]CC(CC)CCCC)=[O:52]>C(OCC)(=O)C.N1C=CC=CC=1.CN(C=O)C.O.C(N(CC)CC)C>[F:9][C:7]1[CH:8]=[C:3]([C:1]2[NH:45][C:51](=[O:52])[O:53][N:2]=2)[CH:4]=[C:5]([F:43])[C:6]=1[N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][N:17]([C@@H:25]([C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH:30]=[CH:29][CH:28]=2)[CH3:26])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:12]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:11]1

Participants

10

Reactant 4

HCID 702EthanolHCID 627832-Ethylhexyl chloroformateHCID 443297Hydroxyamine hydrochlorideHCID 66906160HCID 66906160, compound

Product 1

HCID 136348244HCID 136348244, compound

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 183 mg of tert-butyl {[1-(4-cyano-2,6-difluorophenyl)-3-phenylpiperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate obtained in Example 53 (1), 44 mg of hydroxylamine hydrochloride, and 2 mL of ethanol was added 0.088 mL of triethylamine, and the mixture was stirred for 4 hours while heating under reflux. The mixture was left to be cooled to room temperature, and water was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. This was filtered, and the filtrate was then concentrated under reduced pressure to obtain a residue (colorless foamy substance, 233 mg). To this residue were added 2 mL of DMF and 0.033 mL of pyridine, the mixture was cooled in an ice bath, and then 0.061 mL of 2-ethylhexyl chloroformate was added thereto, followed by stirring for 1 hour while keeping cooling on ice. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine in this order, and the organic layer was then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, to the obtained residue was added 2 mL of xylene, and the mixture was stirred for 5 hours while heating under reflux. This was left to be cooled to room temperature, and then purified by silica gel column chromatography (chloroform/methanol) to obtain 184 mg of tert-butyl ({1-[2,6-difluoro-4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]-3-phenylpiperidin-4-yl}methyl)[(1R)-1-(1-naphthyl)ethyl]carbamate as a yellow foamy substance. ESI+: 641

Workup

  1. temperaturewhile heating
  2. temperatureunder reflux
  3. waitThe mixture was left
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThis was filtered
  8. concentrationthe filtrate was then concentrated under reduced pressure
  9. customto obtain a residue (colorless foamy substance, 233 mg)
  10. temperaturethe mixture was cooled in an ice bath
  11. stirringby stirring for 1 hour
  12. temperaturewhile keeping cooling on ice
  13. washwashed with water and saturated brine in this order
  14. dry with materialthe organic layer was then dried over anhydrous sodium sulfate
  15. filtrationAfter filtration
  16. concentrationthe filtrate was concentrated under reduced pressure, to the obtained residue
  17. additionwas added 2 mL of xylene
  18. stirringthe mixture was stirred for 5 hours
  19. temperaturewhile heating
  20. temperatureunder reflux
  21. waitThis was left
  22. temperatureto be cooled to room temperature
  23. custompurified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-47b420edac6f4a0ba1ab5cc8b6cc8c5a
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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