Potassium Hydroxide → 1-(1-((tert-butoxy)carbonyl)piperidin-4-yl)-1H-pyrazole-4-carboxylic acid

HRID 1186609

Reaction equation

HRID 1186609 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]([O:8]CC)=[O:7])[CH:3]=[N:2]1.[H-].[Na+].CS(O[CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)(=O)=O.[OH-].[K+]>CN(C=O)C.O>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][CH:18]([N:2]2[CH:3]=[C:4]([C:6]([OH:8])=[O:7])[CH:5]=[N:1]2)[CH2:19][CH2:20]1)=[O:25])([CH3:30])([CH3:28])[CH3:29]

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 142179ethyl 1H-pyrazole-4-carboxylateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 534858971-(1-((tert-butoxy)carbonyl)piperidin-4-yl)-1H-pyrazole-4-carboxylic acidYield 40.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 1H-pyrazole-4-carboxylate (700 mg, 5 mmol) and NaH 60% (6 mmol) was stirred under nitrogen at 0° C. for 1 hour in dry DMF (15 mL). tert-Butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (1.53 gr, 5.5 mmol) dissolved in 4 mL of dry DMF was added and the resulting solution was heated at 100° C. overnight. Reaction mixture was quenched with water and extracted (×3) with ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was dissolved in MeOH (20 mL) and water (5 mL) and KOH (1.12 gr, 20 mmol) was added. The resulting solution was stirred at room temperature 24 hours, then solvents removed under reduced pressure. The residue was taken-up with AcOEt and KHSO4 5% solution. Acqueous phase was extracted with EtOAc several times. Collected organic phases were dried with Na2SO4, filtered and evaporated to dryness affording 600 mg of the title compound.

Workup

  1. additionwas added
  2. customReaction mixture
  3. customwas quenched with water
  4. extractionextracted (×3) with ethyl acetate
  5. dry with materialCollected organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. dissolutionResidue was dissolved in MeOH (20 mL)
  9. customsolvents removed under reduced pressure
  10. extractionAcqueous phase was extracted with EtOAc several times
  11. dry with materialCollected organic phases were dried with Na2SO4
  12. filtrationfiltered
  13. customevaporated to dryness

Sources & evidence

ORD record
ord-2c9d1203394746fca46ac41462bb823a
Source dataset
uspto-grants-2014_03
Patent number
US08673893B2

Linked notes

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