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

HRID 2046163

반응식

HRID 2046163 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 73012-Methyltetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f158d740a30b4d62b31f1f6d28ddc7d6
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08592427B2

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