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 10166ノート

反応式

HRID 10166 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-f2c66aeb0d5f475b9780334f93325d54
出典データセット
uspto-grants-2006_08
特許番号
US07094779B2

反応ノート

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