Water → Tert-butyl 4-(4-(ethoxycarbonyl)-1H-pyrazol-1-YL)piperidine-1-carboxylate

HRID 1427009

Reaction equation

HRID 1427009 reaction equation
CS(O[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)(=O)=O.[NH:19]1[CH:23]=[C:22]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:21]=[N:20]1.[H-].[Na+].O>CN(C)C=O.C(OCC)(=O)C>[CH2:27]([O:26][C:24]([C:22]1[CH:23]=[N:19][N:20]([CH:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH:21]=1)=[O:25])[CH3:28]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 45926154Tert-butyl 4-(4-(ethoxycarbonyl)-1H-pyrazol-1-YL)piperidine-1-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate described in Production Example 13-1 (2.7 g, 9.67 mmol) and commercially available ethyl 4-pyrazole carboxylate (1.49 g, 10.6 mmol) were dissolved in N,N-dimethylformamide (30 mL), 50-72% oily sodium hydride (570 mg) was added at 0° C., and the mixture was heated and stirred at 60° C. for 11 hours. The reaction mixture was cooled to room temperature and water and ethyl acetate were added for partition. The organic layer was washed with water twice and then dried over anhydrous sodium sulfate and filtered. The solvent was evaporated, the resultant residue was dissolved in dichloromethane, the resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=4:1-1:1-1:3-0:1), and the target fraction was concentrated under vacuum to obtain the title compound (2.11 g, 68%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customfor partition
  4. washThe organic layer was washed with water twice
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was evaporated
  8. dissolutionthe resultant residue was dissolved in dichloromethane
  9. customthe resultant was purified with silica gel column chromatography (n-heptane:ethyl acetate=4:1-1:1-1:3-0:1)
  10. concentrationthe target fraction was concentrated under vacuum

Sources & evidence

ORD record
ord-c7b0bc050bf042c9b75d2fad693c7bb3
Source dataset
uspto-grants-2015_01
Patent number
US08933099B2

Linked notes

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