Sodium hydride → 1,1-dimethylethyl 4-[3-(methoxycarbonyl)-1H-pyrazol-1-yl]-1-piperidinecarboxylate

HRID 2043761Notes

Reaction equation

HRID 2043761 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:4]1.CS(O[CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)(=O)=O>CN(C)C=O>[CH3:11][O:10][C:8]([C:5]1[CH:6]=[CH:7][N:3]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[N:4]=1)=[O:9]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine2×HCID 178498454HCID 178498454, compound

Product 1

HCID 674641231,1-dimethylethyl 4-[3-(methoxycarbonyl)-1H-pyrazol-1-yl]-1-piperidinecarboxylateYield 23.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 60% dispersion of sodium hydride in mineral oil (192 mg, 4.8 mmol) in 20 mL of N,N-dimethylformamide was cooled to 0° C., and methyl 3-pyrazolecarboxylate (605.37 mg, 4.8 mmol) was gradually added with stirring in nitrogen atmosphere. The reaction mixture was stirred at room temperature for 0.5 h and cooled again to 0° C. A solution of 1,1-dimethylethyl 4-[(methylsulfonyl)oxy]-1-piperidine-carboxylate (1.18 g, 4 mmol) (i.e. the product of Example 18, Step A) in 5 mL of N,N-dimethylformamide was gradually added to the reaction mixture. The resulting mixture was stirred for 5 days at 60° C. The reaction mixture was poured in ice water and extracted with ethyl acetate. The organic layer was dried (MgSO4), evaporated in vacuo, and purified by medium-pressure liquid chromatography on silica gel eluting with 0-10% methanol in ethyl acetate as eluant to give 290 mg of the title compound as a white solid.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 0.5 h
  2. temperaturecooled again to 0° C
  3. stirringThe resulting mixture was stirred for 5 days at 60° C
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customevaporated in vacuo
  7. custompurified by medium-pressure liquid chromatography on silica gel eluting with 0-10% methanol in ethyl acetate as eluant

Sources & evidence

ORD record
ord-5676256836444b88a770c0067ded6991
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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