Dimethylformamide → 1-[4-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanone

HRID 1955845Notes

Reaction equation

HRID 1955845 reaction equation
Cl.[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[N:8][O:9][C:5]=2[CH:4]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=1[O:37][CH3:38].CN(C)C=O>O>[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:11][CH2:12][N:13]([CH2:25][CH2:26][O:27][C:28]4[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=4[O:37][CH3:38])[CH2:14][CH2:15]3)=[N:8][O:9][C:5]=2[CH:4]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11334359R-56109 hydrochlorideHCID 144071701-[4-(2-Chloroethoxy)-3-methoxyphenyl]ethanone

Product 1

HCID 104318121-[4-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]ethoxy]-3-methoxyphenyl]ethanoneYield 48.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A stirred mixture of 6-fluoro-3(4-piperidinyl)-1,2 benzisoxazole hydrochloride (5.1 g, 20 mmol), K2CO3 (5.2 g), 1-[4-(2chloroethoxy)-3-methoxyphenyl]ethanone (5.0 g, 1022 mmol), and dimethylformamide (90 ml) was heated at 90 f° C. or 16 hours. The reaction was poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate was washed (water), dried (MgSO4) and concentrated to afford 7.4 of a yellow solid. The solid was chromatographed on a Waters Prep LC 500 utilizing dichloromethane/methanol (4%) as eluent, and subsequent concentration of the appropriate fraction afforded 4.0 g of a yellow solid. The solid was recrystallized from ethyl alcohol to yield 3.1 g (38%) of 1-[4-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperindyl]ethoxy]-3-methoxyphenyl]ethanone, as slightly yellow flakes, m.p.=132°-134° C.

Workup

  1. temperaturewas heated at 90 f° C
  2. custom16 hours
  3. extractionthe aqueous mixture was extracted with ethyl acetate
  4. washThe ethyl acetate was washed (water)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto afford 7.4 of a yellow solid
  8. customThe solid was chromatographed on a Waters Prep LC 500 utilizing dichloromethane/methanol (4%) as eluent
  9. concentrationsubsequent concentration of the appropriate fraction

Sources & evidence

ORD record
ord-e16e380fd3eb45859af041e8100c5ab5
Source dataset
uspto-grants-1998_07
Patent number
US05776963

Reaction notes

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