Sodium Acetate → 1-{(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazin-4-yl}-2-propanone O-[2-(dimethylamino)-ethyl]oxime

HRID 10166Notes

Reaction equation

HRID 10166 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15](=O)[CH3:16])[CH2:10][C@H:9]1[CH2:18][C:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[NH:21][CH:20]=1)=[O:7].Cl.Cl.[CH3:39][N:40]([CH3:45])[CH2:41][CH2:42][O:43][NH2:44].C([O-])(=O)C.[Na+]>CO>[CH3:39][N:40]([CH3:45])[CH2:41][CH2:42][O:43][N:44]=[C:15]([CH3:16])[CH2:14][N:11]1[CH2:12][CH2:13][N:8]([C:6](=[O:7])[C:5]2[CH:4]=[C:3]([C:2]([F:36])([F:35])[F:1])[CH:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=2)[C@H:9]([CH2:18][C:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][CH:20]=2)[CH2:10]1

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 10176354O-[2-(dimethylamino)ethyl]hydroxylamine dihydrochlorideHCID 86594235(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(2-propanon-1-yl)piperazine

Product 1

HCID 865942341-{(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazin-4-yl}-2-propanone O-[2-(dimethylamino)-ethyl]oximeYield 104%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(2-propanon-1-yl)piperazine (255 mg), O-[2-(dimethylamino)ethyl]hydroxylamine dihydrochloride (89 mg), sodium acetate (catalytically), and methanol (10 mL) was heated under reflux for 2 h. The solvent was removed in vacuo, and the residue was treated with dichloromethane and NAOH (aq, 2N). The layers were separated, the organic layer was dried and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH/NH4OH 92/7.5/0.5) to afford 1-{(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-piperazin-4-yl}-2-propanone O-[2-(dimethylamino)-ethyl]oxime 0.31 g (>95%) as an E/Z mixture. Rf 0.26 (CH2Cl2/MeOH/NH4OH 92/7.5/0.5).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 h
  3. customThe solvent was removed in vacuo
  4. additionthe residue was treated with dichloromethane and NAOH (aq, 2N)
  5. customThe layers were separated
  6. customthe organic layer was dried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH/NH4OH 92/7.5/0.5)

Sources & evidence

ORD record
ord-f2c66aeb0d5f475b9780334f93325d54
Source dataset
uspto-grants-2006_08
Patent number
US07094779B2

Reaction notes

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