Benzyl Bromide → ethyl 2-benzyl-5-(4-benzyloxyphenyl)-2H-pyrazole-3-carboxylate

HRID 322928Notes

Reaction equation

HRID 322928 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[NH:18][N:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O1CCCC1>[CH2:27]([N:18]1[C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:16][C:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:14][CH:13]=2)=[N:19]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[CH2:27]([N:19]1[C:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:14][CH:13]=2)=[CH:16][CH:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[NH:18]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 22010318Ethyl 5-(4-benzyloxyphenyl)-2H-pyrazole-3-carboxylate

Product 2

HCID 22010441ethyl 2-benzyl-5-(4-benzyloxyphenyl)-2H-pyrazole-3-carboxylateHCID 70226768ethyl 1-benzyl-5-(4-benzyloxyphenyl)-2H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 5-(4-benzyloxyphenyl)-2H-pyrazole-3-carboxylate (6 g) is added portionwise to a stirred suspension of sodium hydride (0.75 g) in tetrahydrofuran (250 mL) at room temperature. Stirring is continued at this temperature for a further 30 minutes when benzyl bromide (3.57 g) is added in one portion. The reaction mixture is heated to reflux for 5 hours, then evaporated in vacuo. The residue is treated with water (250 mL), the resulting yellow solid washed well with water, then dissolved in tetrahydrofuran and filtered to remove a small amount of insoluble white solid. The filtrate is evaporated and the residual yellow solid purified by flash chromatography on silica eluting initially with dichloromethane then with a mixture of ethyl acetate and dichloromethane (1:9 v/v) to give ethyl 2-benzyl-5-(4-benzyloxyphenyl)-2H-pyrazole-3-carboxylate (1.2 g) and ethyl 1-benzyl-5-(4-benzyloxyphenyl)-2H-pyrazole-3-carboxylate (2 g).

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux for 5 hours
  3. customevaporated in vacuo
  4. additionThe residue is treated with water (250 mL)
  5. washthe resulting yellow solid washed well with water
  6. dissolutiondissolved in tetrahydrofuran
  7. filtrationfiltered
  8. customto remove a small amount of insoluble white solid
  9. customThe filtrate is evaporated
  10. customthe residual yellow solid purified by flash chromatography on silica eluting initially with dichloromethane
  11. additionwith a mixture of ethyl acetate and dichloromethane (1:9 v/v)

Sources & evidence

ORD record
ord-095f95a498844821b05002d622e39367
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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