Acetonitrile → 6-Fluoro-3-[1-[3-[(1H-indol-4-yl)oxy]propyl]-4-piperidinyl]-1,2-benzisoxazole

HRID 363631노트

반응식

HRID 363631 반응식
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:29]=1[CH:30]=[CH:31][NH:32]2.CC#N>O>[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:24][CH2:25][CH2:26][O:27][C:28]4[CH:36]=[CH:35][CH:34]=[C:33]5[C:29]=4[CH:30]=[CH:31][NH:32]5)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 11430Potassium Carbonate2회HCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 116941694-(3-chloropropoxy)-1H-indole

생성물 1

HCID 158169466-Fluoro-3-[1-[3-[(1H-indol-4-yl)oxy]propyl]-4-piperidinyl]-1,2-benzisoxazole수율 103.5%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.5 g, 16 mmol), K2CO3 (2.2 g, 16 mmol), KI (200 mg), 4-(3-chloropropoxy)indole (3.0 g, 14 mmol) and CH3CN (100 ml) was stirred at reflux under N2 for 7 hours and then at ambient temperature for 68 hours. Reflux was resumed for an additional 6 hours whereupon a TLC revealed incomplete reaction. K2CO3 (0.5 g, 4 mmol) was added and the reaction was stirred at reflux for 17 hours. The cooled reaction was poured into H2O and the aqueous mixture was extracted with EtOAc. The organic extract was washed with H2O and saturated NaCl and after drying over MgSO4 the solvent was removed to afford 5.7 g of a beige solid. The product was purified by preparative HPLC (Water's Associates Prep LC/System 500 using 2 silica gel columns and 4% MeOH-CH2Cl2 as eluent) to yield 3.4 g (61%) of a beige solid. Two consecutive recrystallizations from EtOH provided 2.3 g (41%) of a white powder, m.p.=129°-131° C.

후처리

  1. temperatureat reflux under N2 for 7 hours
  2. temperatureReflux
  3. waitwas resumed for an additional 6 hours whereupon a TLC
  4. customreaction
  5. stirringthe reaction was stirred
  6. temperatureat reflux for 17 hours
  7. customThe cooled reaction
  8. extractionthe aqueous mixture was extracted with EtOAc
  9. extractionThe organic extract
  10. washwas washed with H2O and saturated NaCl
  11. dry with materialafter drying over MgSO4 the solvent
  12. customwas removed

출처 및 근거

ORD 기록
ord-3561ffe5e1af4a519725e97d228f7920
출처 데이터셋
uspto-grants-1999_02
특허 번호
US05874435

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