Acetonitrile → 4-[3-[4-(6-Fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl]propoxy]-3-hydroxyphenyl ethanone

HRID 1533367Notes

Reaction equation

HRID 1533367 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][S:8][C:4]=2[CH:3]=1.Cl[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][C:23]=1[OH:31].C([O-])(O)=O.[Na+].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]([CH2:18][CH2:19][CH2:20][O:21][C:22]4[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][C:23]=4[OH:31])[CH2:13][CH2:14]3)=[N:7][S:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 516892Sodium BicarbonateHCID 103765071-(4-(3-Chloropropoxy)-3-hydroxyphenyl]ethanoneHCID 185049766-Fluoro-3-(4-piperidinyl)-1,2-benzisothiazole

Product 1

HCID 219600124-[3-[4-(6-Fluoro-1,2-benzisothiazol-3-yl)-1-piperidinyl]propoxy]-3-hydroxyphenyl ethanoneYield 97%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisothiazole (2.4 g, 10.1 mmol), 1-[4-(3-chloropropoxy)-3hydroxyphenyl] ethanone (2.5 g, 11.1 mmol), NaHCO3, (0.94 g, 11.1 mmol), KI (100 mg) and CH3CN (100 ml) was stirred at reflux under N2 for 65 hours. The cooled reaction was poured into H2O and the aqueous mixture was extracted with EtOAc. The EtOAc extract was washed with H2O (1x) and brine (3x) and after drying with MgSO4 the solvent was evaporated to give 4.2 g of a dark solid. Three consecutive recrystallizations from EtOH provided 2.1 g (48%) of glittery beige crystals m.p.=135-137° C.

Workup

  1. temperatureat reflux under N2 for 65 hours
  2. customThe cooled reaction
  3. extractionthe aqueous mixture was extracted with EtOAc
  4. extractionThe EtOAc extract
  5. washwas washed with H2O (1x) and brine (3x)
  6. dry with materialafter drying with MgSO4 the solvent
  7. customwas evaporated

Sources & evidence

ORD record
ord-54d38d65f38f48e296834c55bcf51990
Source dataset
uspto-grants-2001_03
Patent number
US06207680B1

Reaction notes

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