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

HRID 1640998Notes

Reaction equation

HRID 1640998 reaction equation
C([O:3][C:4]([C:6]1[CH:7]=[N:8][NH:9][CH:10]=1)=[O:5])C.[H-].[Na+].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23](OS(C)(=O)=O)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[OH-].[Na+]>CN(C)C=O.O.CO>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([N:9]2[CH:10]=[C:6]([C:4]([OH:3])=[O:5])[CH:7]=[N:8]2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 4

HCID 14798Sodium 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%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of 1H-pyrazole-4-carboxylic acid ethyl ester (701 mg, 5 mmol) in dry N,N-dimethylformamide (15 mL) at 0-5° C., under argon, was added 60% sodium hydride (480 mg, 1.2 eq). After stirring for 1 hour was added a solution of 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (1.53 g, 1.1 eq) in dry N,N-dimethylformamide (4 mL). The mixture was heated to 100° C., stirred for 6 hours then treated with water and extracted with ethyl acetate. The organic layer was separated (organic layer A). The aqueous layer was acidified with a 5% aqueous solution of potassium bisulfate and extracted with ethyl acetate giving, after separation, the organic layer B. The organic layer A was evaporated to dryness. The residue was treated with 20 mL of methanol, 5 mL of water and 1.12 g of sodium hydroxide (20 mmol) and stirred at room temperature for 2 days. The solvents were removed under reduced pressure, the residue treated with ethyl acetate and washed with 5% aqueous solution of potassium bisulfate giving the organic layer C. The combined organic layers B and C were dried over sodium sulfate and evaporated to dryness. The residue was triturated with diethyl ether and dried under vacuum affording 590 mg of title compound.

Workup

  1. stirringstirred for 6 hours
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was separated (organic layer A)
  4. extractionextracted with ethyl acetate giving
  5. customafter separation
  6. customThe organic layer A was evaporated to dryness
  7. stirringstirred at room temperature for 2 days
  8. customThe solvents were removed under reduced pressure
  9. additionthe residue treated with ethyl acetate
  10. washwashed with 5% aqueous solution of potassium bisulfate giving the organic layer C
  11. dry with materialThe combined organic layers B and C were dried over sodium sulfate
  12. customevaporated to dryness
  13. customThe residue was triturated with diethyl ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-b65eb23181cd41dfb1ab81a79a1b1ee3
Source dataset
uspto-grants-2012_02
Patent number
US08114865B2

Reaction notes

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