Acetonitrile → 6-Fluoro3-[1-[3-[(1H-indol-5-yl)oxy]propyl]-4-piperidinyl]-1,2-benzisoxazole

HRID 357407Notes

Reaction equation

HRID 357407 reaction equation
[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:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH:32]=[CH:31]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:29]=[C:30]5[C:34](=[CH:35][CH:36]=4)[NH:33][CH:32]=[CH:31]5)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 114994555-(3-Chloro-propoxy)-1H-indole

Product 1

HCID 158169476-Fluoro3-[1-[3-[(1H-indol-5-yl)oxy]propyl]-4-piperidinyl]-1,2-benzisoxazoleYield 123.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.6 g, 11.8 mmol), K2CO3 (1.6 g, 11.6 mmol), KI (200 mg), 5-(3-chloropropoxy)indole (2.2 g, 10.5 mmol) and CH3CN (100 ml) was stirred at reflux under N2 for 18 hours. The cooled reaction was poured into H2O and the aqueous mixture was extracted with EtOAc. The EtOAc extract was washed 2 times with H2O, 2 times with brine and after drying with MgSO4 the solvent was removed in vacuo to yield 5.1 g of a dark oil. The oil was purified by preparative HPLC (Water's Associates Prep LC/System 500, using 2 silica gel columns and 4% MeOH--CH2Cl2 as eluent) to afford 2.65 g (65%) of a beige solid. Recrystallization from ethanol gave 2.2 g (54%) of a beige powder, m.p.=118°-121° C.

Workup

  1. temperatureat reflux under N2 for 18 hours
  2. customThe cooled reaction
  3. extractionthe aqueous mixture was extracted with EtOAc
  4. extractionThe EtOAc extract
  5. washwas washed 2 times with H2O, 2 times with brine
  6. dry with materialafter drying with MgSO4 the solvent
  7. customwas removed in vacuo

Sources & evidence

ORD record
ord-6ff8cee748a244f89bd2150311d23a06
Source dataset
uspto-grants-1998_11
Patent number
US05840727

Reaction notes

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