Sodium hydride → chloro(phenyl)methyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1518670ノート

反応式

HRID 1518670 の反応式
[CH:1]1[CH:2]=[C:3]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]4[CH2:30][CH2:29][C:27](=[O:28])[NH:26][C:24]=4[CH:25]=3)[CH2:11][CH2:10]2)[C:4]([Cl:8])=[C:5]([Cl:7])[CH:6]=1.[H-].[Na+].[C:33](Cl)(=[O:43])[O:34][CH:35]([Cl:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CC1CCCO1.C(OCC)(=O)C>[Cl:8][C:4]1[C:5]([Cl:7])=[CH:6][CH:1]=[CH:2][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[C:24]3[C:23]([CH2:30][CH2:29][C:27](=[O:28])[N:26]3[C:33]([O:34][CH:35]([Cl:42])[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[O:43])=[CH:22][CH:21]=2)[CH2:11][CH2:10]1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 60795AripiprazoleHCID 14320655Chloro(phenyl)methyl carbonochloridate

生成物 1

HCID 66815335chloro(phenyl)methyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

試薬・触媒・溶媒 2

HCID 73012-Methyltetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a suspension of aripiprazole (1 g, 2.23 mmol) in 2-methyltetrahydrofuran (20 mL) was added NaH (178 mg, 4.46 mmol). The reaction was heated to reflux for 1.5 hours then cooled to room temperature. Chloro(phenyl)methyl carbonochloridate (1.37 g, 6.69 mmol) was then added and the reaction stirred overnight at room temperature. The reaction was cooled to 0° C., diluted with ethyl acetate (20 mL) and quenched with aqueous saturated NaHCO3 (20 mL) solution. The reaction was extracted with ethyl acetate (3×20 mL) and the combined organics washed with brine (50 mL), then dried (MgSO4) and concentrated to give chloro(phenyl)methyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate (crude yield 2.10 g) as a 1:3 mixture of product/aripiprazole. The product was taken onto the next step crude.

後処理

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 1.5 hours
  3. temperatureThe reaction was cooled to 0° C.
  4. customquenched with aqueous saturated NaHCO3 (20 mL) solution
  5. extractionThe reaction was extracted with ethyl acetate (3×20 mL)
  6. washthe combined organics washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-970e7201ef9d4c48882fa491d6bdefd6
出典データセット
uspto-grants-2015_07
特許番号
US09072788B2

反応ノート

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