Acetonitrile → HCID 10025444, compound

HRID 2256530Notes

Reaction equation

HRID 2256530 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][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=1[NH:37][CH3:38].C(#N)C>CO.C(Cl)Cl.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][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=4[NH:37][CH3:38])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 103319421-[4-(3-Chloropropoxy)-3-methylaminophenyl]ethanone

Product 1

HCID 10025444HCID 10025444, compoundYield 47.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.3 g, 10.3 mmol), K2CO3 (1.4 g, 10.3 mmol), 1-[4-(3-chloropropoxy)-3-(methylamino)phenyl]ethanone (2.5 g, 10.3 mmol), KI (0.10 g), and acetonitrile (100 ml) was stirred at reflux under nitrogen for 23 hours. The reaction was cooled to ambient temperature, poured into water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed twice with water, dried with MgSO4 and was concentrated to yield 4.8 g of a damp, brown solid. The compound was isolated by preparative HPLC (Waters Associates prep LC/System 500, utilizing 2 silica gel columns and 4% methanol-methylene chloride as eluent). Concentration of appropriate fractions afforded 2.4 g. Recrystallization from ethanol gave 2.1 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-(methylamino)phenyl]ethanone as a beige solid, m.p.=151°-153° C.

Workup

  1. temperatureat reflux under nitrogen for 23 hours
  2. extractionthe aqueous mixture was extracted with ethyl acetate
  3. extractionThe ethyl acetate extract
  4. washwas washed twice with water
  5. dry with materialdried with MgSO4
  6. concentrationwas concentrated
  7. customto yield 4.8 g of a damp, brown solid
  8. customConcentration of appropriate fractions afforded 2.4 g
  9. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-00b68e670a514978ad49ea5c6402689c
Source dataset
uspto-grants-1997_08
Patent number
US05654319

Reaction notes

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