Dimethylformamide → 1-(4-Bromobenzyl)-5-propyl-1H-pyrazole-3-carboxylic Acid Ethyl Ester
Reaction equation
[CH2:1]([C:4]1[CH:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[NH:6][N:5]=1)[CH2:2][CH3:3].[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>>[CH2:12]([O:11][C:9]([C:7]1[CH:8]=[C:4]([CH2:1][CH2:2][CH3:3])[N:5]([CH2:19][C:18]2[CH:21]=[CH:22][C:15]([Br:14])=[CH:16][CH:17]=2)[N:6]=1)=[O:10])[CH3:13]Participants
Procedure
Ethyl 3-n-propylpyrazole-5-carboxylate (8.0 g, 43.0 mmol), 4-bromobenzyl bromide (11.0 g, 43.0 mmol) and potassium carbonate (5.9 g, 43.0 mmol) were dissolved in DMF (433 mL, 5590 mmol). The resulting suspension was stirred at room temperature over approximately 48 hours. The material was concentrated, then diluted with aqueous NaHCO3 and diethyl ether. The aqueous layer was further extracted with diethyl ether. The combined organics were dried over MgSO4, filtered and concentrated. The residue was purified using flash chromatography (1st 40:1 hexanes/EtOAc; 2nd 5:1 hexanes/EtOAc). The two isomers were separated and analyzed by NMR and NOE: 1-(4-bromobenzyl)-5-propyl-1H-pyrazole-3-carboxylic acid ethyl ester (5.7 g) and 2-(4-bromobenzyl)-5-propyl-2H-pyrazole-3-carboxylic acid ethyl ester.
Workup
- concentrationThe material was concentrated
- additiondiluted with aqueous NaHCO3 and diethyl ether
- extractionThe aqueous layer was further extracted with diethyl ether
- dry with materialThe combined organics were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified
- customThe two isomers were separated
Sources & evidence
- ORD record
- ord-efb4cf8e668a415ebd91fe6ae44add28
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822522B2
Reaction notes
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