Tetrahydrofuran → 2-(2,4-Dimethoxy-benzyl)-4-(3-morpholin-4-yl-propoxy)-2,3-dihydro-1H-isoindole

HRID 41415

반응식

HRID 41415 반응식
[CH3:1][O:2][C:3]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:4]=1[CH2:5][N:6]1[C:14](=O)[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:16][CH2:17][CH2:18][CH2:19][N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[C:7]1=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1>>[CH3:1][O:2][C:3]1[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][C:4]=1[CH2:5][N:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:16][CH2:17][CH2:18][CH2:19][N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH2:7]1

참가 물질

4

반응물 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 592631552-(2,4-Dimethoxy-benzyl)-4-(3-morpholin-4-yl-propoxy)-isoindole-1,3-dione

생성물 1

HCID 592631052-(2,4-Dimethoxy-benzyl)-4-(3-morpholin-4-yl-propoxy)-2,3-dihydro-1H-isoindole수율 83.1%

실험 절차

2-(2,4-Dimethoxy-benzyl)-4-(3-morpholin-4-yl-propoxy)-isoindole-1,3-dione (298 mg, 0.68 mmol) was treated with a 1M solution of lithium aluminium hydride in THF (5 mL, 5 mmol) and maintained at r.t. for 21 hours. The mixture was heated to 75° C. for 1 hour then cooled in ice and quenched by the dropwise addition of water (0.2 mL), 2N sodium hydroxide solution (0.4 mL) and water (0.4 mL). Magnesium sulfate was added, followed by ethyl acetate and then the mixture was stirred at r.t. for 1 hour. The solids were removed by filtration, being well washed with ethyl acetate. Concentration of the filtrate gave a crude product which was purified by flash chromatography on silica, eluting with 5% methanol in DCM. This afforded the title compound (233 mg, 83%) as a red oil. 1H NMR (methanol-d4) 7.24 (1H, d), 7.15 (1H, t), 6.80 (1H, d), 6.78 (1H, d), 6.56 (1H, d), 6.52 (1H, dd), 4.05 (2H, t), 3.94 (2H, s), 3.88 (2H, s), 3.87 (2H, s), 3.83 (3H, s), 3.80 (3H, s), 3.70-3.68 (4H, m), 2.54-2.50 (2H, m), 2.49-2.47 (4H, m), 2.00-1.93 (2H, m). MS: [M+H]+ 413.

후처리

  1. temperatureThe mixture was heated to 75° C. for 1 hour
  2. temperaturethen cooled in ice
  3. customquenched by the dropwise addition of water (0.2 mL), 2N sodium hydroxide solution (0.4 mL) and water (0.4 mL)
  4. additionMagnesium sulfate was added
  5. customThe solids were removed by filtration
  6. washbeing well washed with ethyl acetate
  7. customConcentration of the filtrate gave a crude product which
  8. customwas purified by flash chromatography on silica
  9. washeluting with 5% methanol in DCM

출처 및 근거

ORD 기록
ord-359dc340a3594939842635d307da2266
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530469B2

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