Trifluoroacetic acid → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine

HRID 584198Notes

Reaction equation

HRID 584198 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]([O:23]C(C)(C)C)=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[C:31]([CH3:36])[CH:30]=1)=[O:7].FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[F:43][C:40]([F:41])([F:42])[C:38]1[CH:37]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:45])[F:44])[CH:39]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]([OH:23])=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[C:31]([CH3:36])[CH:30]=1)=[O:7]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86596439(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(tert-butoxycarbonylmethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine

Product 1

HCID 54368795(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazineYield 101.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(tert-butoxycarbonylmethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine (425 mg) in dichloromethane (2.5 ml) was treated with trifluoroacetic acid (2.5 ml) at room temperature for 1 hour. The mixture was adjusted to pH 7.4 with aqueous sodium bicarbonate solution and evaporated under reduced pressure. The residue was washed with a mixture of dichloromethane and methanol (9:1), and the solution was evaporated under reduced pressure and purified by column chromatography on a silica gel using a mixture of methanol and chloroform (1:9) as eluent and subsequent crystallization from ethyl acetate, isopropyl ether, and hexane to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine (395 mg) as a white powder.

Workup

  1. customevaporated under reduced pressure
  2. washThe residue was washed with a mixture of dichloromethane and methanol (9:1)
  3. customthe solution was evaporated under reduced pressure
  4. custompurified by column chromatography on a silica gel using
  5. additiona mixture of methanol and chloroform (1:9) as eluent
  6. customsubsequent crystallization from ethyl acetate, isopropyl ether, and hexane

Sources & evidence

ORD record
ord-0e9a345eff5a4ba1845d942263400153
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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