Acetonitrile → 6-Fluoro-3-[1-(3-phenoxypropyl)-4-piperidinyl]1,2-benzisoxazole

HRID 1601204Notes

Reaction equation

HRID 1601204 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:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(#N)C>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:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 76917(3-Chloropropoxy)benzeneHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 104733206-Fluoro-3-[1-(3-phenoxypropyl)-4-piperidinyl]1,2-benzisoxazoleYield 47%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (4.0 g, 18.2 mmol), K2CO3 (3.0 g, 21.8 mmol), KI (100 mg), 3-chloropropoxybenzene (3.4 g, 20.0 mmol), and acetonitrile was stirred at reflux under nitrogen for 30 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with brine, dried with MgSO4 and concentrated to afford 6.2 g of a damp, beige solid. The compound was recrystallized twice from ethanol to yield (47%) of 6-fluoro-3-[1-(3-phenoxypropyl)-4-piperidinyl]-1,2-benzisoxazole as a light beige solid, m.p.=78-80° C.

Workup

  1. temperatureat reflux under nitrogen for 30 hours
  2. extractionthe aqueous mixture was extracted with ethyl acetate
  3. extractionThe ethyl acetate extract
  4. washwas washed with brine
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated
  7. customto afford 6.2 g of a damp, beige solid
  8. customThe compound was recrystallized twice from ethanol

Sources & evidence

ORD record
ord-3b1711e3d9e948079b39047604818f79
Source dataset
uspto-grants-1999_11
Patent number
US05977113

Reaction notes

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