1-(tert-Butoxycarbonyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]piperidine-3-carboxylic acid → Tert-butyl 3-(3-ethoxy-1,2,4-oxadiazol-5-yl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]piperidine-1-carboxylate

HRID 661289Notes

Reaction equation

HRID 661289 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[C:16]([F:25])[CH:15]=2)[CH2:11][CH:10]([C:26](O)=[O:27])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:30]=[C:31]([O:33][CH2:34][CH3:35])[NH2:32]>O1CCOCC1.CN(C=O)C>[CH2:34]([O:33][C:31]1[N:32]=[C:26]([CH:10]2[CH2:11][CH:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:23])([F:24])[F:22])=[C:16]([F:25])[CH:15]=3)[CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9]2)[O:27][N:30]=1)[CH3:35]

Participants

5

Reactant 2

HCID 581165141-(tert-Butoxycarbonyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]piperidine-3-carboxylic acidHCID 76223295ethyl N-hydroxyimidocarbamate

Product 1

HCID 58116493Tert-butyl 3-(3-ethoxy-1,2,4-oxadiazol-5-yl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

442 mg (1.09 mmol) of 1-(tert-butoxycarbonyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-piperidine-3-carboxylic acid were dissolved in 11.8 ml of dioxane and 5.9 ml of DMF, heated to 60° C. and admixed with 264 mg (1.63 mmol) of 1,1″-carbonyldiimidazole. The reaction mixture was stirred at this temperature for three hours and then admixed with 170 mg (1.63 mmol) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390]. The mixture was left to stir at 50° C. for one hour and thereafter at 115° C. for nine hours. The reaction mixture was concentrated under reduced pressure, taken up in ethyl acetate and washed three times with water. The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. Yield: 387 mg (75% of theory, purity 61%)

Workup

  1. waitThe mixture was left
  2. stirringto stir at 50° C. for one hour
  3. waitat 115° C. for nine hours
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. washwashed three times with water
  6. dry with materialThe organic phase was dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2133b772133d462a9f049ba2dd982d1d
Source dataset
uspto-grants-2011_12
Patent number
US08084469B2

Reaction notes

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