Pyrazole → 3-Pyrazol-1-ylmethyl-azetidine-1-carboxylic acid tert-butyl ester

HRID 528753Notes

Reaction equation

HRID 528753 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[H-].[Na+].[C:8]([O:12][C:13]([N:15]1[CH2:18][CH:17]([CH2:19]OS(C)(=O)=O)[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]>C1COCC1>[C:8]([O:12][C:13]([N:15]1[CH2:18][CH:17]([CH2:19][N:1]2[CH:5]=[CH:4][CH:3]=[N:2]2)[CH2:16]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 1048PyrazoleHCID 24758Sodium hydrideHCID 21959416Tert-butyl 3-((methanesulfonyloxy)methyl)azetidine-1-carboxylate

Product 1

HCID 679792833-Pyrazol-1-ylmethyl-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 17.9 mg (0.26 mmol) pyrazole in 2 mL dry THF at 0° C. was added 14 mg (0.35 mmol, 60% dispersion in mineral oil) NaH and the reaction was stirred for 30 minutes. 50 mg (0.17 mmol) 3-methanesulfonyloxymethyl-azetidine-1-carboxylic acid tert-butyl ester in 1 mL dry THF was added dropwise and the reaction was allowed to warm to room temperature for 16 hours. The solvent was evaporated and the remaining residue was partitioned between 25 mL H2O and 25 mL EtOAc. The organic phase was washed with 25 mL 1% citric acid solution, H2O (3×25 mL), 25 mL brine and dried with Na2SO4. After filtration and evaporation of the solvent the product was used in the next step without further purification.

Workup

  1. customThe solvent was evaporated
  2. customthe remaining residue was partitioned between 25 mL H2O and 25 mL EtOAc
  3. washThe organic phase was washed with 25 mL 1% citric acid solution, H2O (3×25 mL), 25 mL brine
  4. dry with materialdried with Na2SO4
  5. filtrationAfter filtration and evaporation of the solvent the product
  6. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-ac768b0553a24003b73c7895ccfea3d7
Source dataset
uspto-grants-2016_05
Patent number
US09346816B2

Reaction notes

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