Sodium Bicarbonate → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine

HRID 584188Notes

Reaction equation

HRID 584188 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([CH3:22])[CH:16]=1)=[O:7].[CH:32]([C:34]1[CH:35]=[N:36][N:37](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:38]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:32][C:34]2[CH:35]=[N:36][NH:37][CH:38]=2)[CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([CH3:22])[CH:16]=1)=[O:7]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 223425751-Trityl-1H-pyrazole-4-carbaldehydeHCID 54478438(2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine

Product 1

HCID 54247854(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazineYield 64.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine (3.71 g) and 4-formyl-1-(triphenylmethyl)pyrazole (3.66 g) in 1,2-dichloroethane (80 ml) was added sodium triacetoxyborohydride (2.86 g). After stirring at room temperature for 3 hours, aqueous sodium bicarbonate solution was added to the mixture and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was dissolved in dichloromethane (40 ml) and added to a mixture of trifluoroacetic acid (30 ml) and anisole (15 ml). After stirring for 7.5 hours at room temperature, the mixture was quenched with 10% sodium hydroxide (150 ml) and aqueous sodium bicarbonate and extracted with dichloromethane. The extract was washed with aqueous sodium bicarbonate solution and brine successively, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (3:7) to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine (2.84 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. dissolutionThe resulting residue was dissolved in dichloromethane (40 ml)
  6. additionadded to a mixture of trifluoroacetic acid (30 ml) and anisole (15 ml)
  7. stirringAfter stirring for 7.5 hours at room temperature
  8. customthe mixture was quenched with 10% sodium hydroxide (150 ml) and aqueous sodium bicarbonate
  9. extractionextracted with dichloromethane
  10. washThe extract was washed with aqueous sodium bicarbonate solution and brine successively
  11. dry with materialdried over magnesium sulfate
  12. customevaporated under reduced pressure
  13. customThe residue was purified by column chromatography on silica gel using
  14. additiona mixture of ethyl acetate and hexane (3:7)

Sources & evidence

ORD record
ord-aa7f1fa3362c4960a23029d6515c6541
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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