Water → ((R)-1-methyl-2-pyrazol-1-yl-ethyl)-carbamic acid tert-butyl ester

HRID 246120Notes

Reaction equation

HRID 246120 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[H-].[Na+].[C:8]([O:12][C:13]([NH:15][C@H:16]([CH3:23])[CH2:17]OS(C)(=O)=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].O>CN(C=O)C.C(OCC)(=O)C>[C:8]([O:12][C:13](=[O:14])[NH:15][C@H:16]([CH3:17])[CH2:23][N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1)([CH3:11])([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 962WaterHCID 1048PyrazoleHCID 24758Sodium hydrideHCID 14427185(R)-2-((tert-butoxycarbonyl)amino)propyl methanesulfonate

Product 1

HCID 71279609((R)-1-methyl-2-pyrazol-1-yl-ethyl)-carbamic acid tert-butyl esterYield 72.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1H-Pyrazole (70 mg, 1.03 mmol) was dissolved in DMF (5 ml) and cooled in an ice bath. Sodium hydride (60% dispersion in mineral oil, 41 mg, 1.03 mmol) was added and the reaction was stirred for 15 min. Methanesulfonic acid (R)-2-tert-butoxycarbonylamino-propyl ester (200 mg, 0.79 mmol) was then added and the mixture was stirred at 50° C. for 16 h. The reaction was cooled to room temperature and water and ethyl acetate were added. The aqueous layer was extracted twice more with ethyl acetate and the combined organic layers were washed with sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to give 129 mg (72%) of ((R)-1-methyl-2-pyrazol-1-yl-ethyl)-carbamic acid tert-butyl ester. (M+H)+=226.

Workup

  1. temperaturecooled in an ice bath
  2. stirringthe mixture was stirred at 50° C. for 16 h
  3. extractionThe aqueous layer was extracted twice more with ethyl acetate
  4. washthe combined organic layers were washed with sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. customAfter evaporation
  7. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-fc0201827b444749b2a1a842c56c150f
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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