Iloperidone → 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-phenyl]ethanone Oxime

HRID 2184519Notes

Reaction equation

HRID 2184519 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]4[CH:24]=[CH:23][C:22]([C:25](=O)[CH3:26])=[CH:21][C:20]=4[O:28][CH3:29])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.Cl.[NH2:33][OH:34].C([O-])(=O)C.[NH4+].C(O)C.O>O>[F:1][C:2]1[CH:31]=[CH:30][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]4[CH:24]=[CH:23][C:22]([C:25](=[N:33][OH:34])[CH3:26])=[CH:21][C:20]=4[O:28][CH3:29])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 71360IloperidoneHCID 443297Hydroxyamine hydrochlorideHCID 517165Ammonium AcetateHCID 19096565Water ethanol

Product 1

HCID 738566991-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-phenyl]ethanone Oxime

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-piperidinyl]propoxy]-3-methoxyphenyl]ethanone (4.3 g, 10 mmol), prepared as in Example 3 above, hydroxylamine hydrochloride (1.3 g, 18 mmol), ammonium acetate (1.7 g, 22 mmol) and ethanol-H2O was stirred and refluxed for 16 hours. The reaction was poured into water, and the mixture was cooled in an ice bath for 2 hours. The resultant, white solid was collected washed with water, and dried to yield 4,6 g or hydrochloride salt of the oxime, m.p.=216°-218° C. The compound was dispersed in water, and ammonium hydroxide was added until the suspension was decidedly basic. The basic suspension was then extracted with dichloromethane, and after washing with water, drying (MgSO4) and concentrating the extract, 3.0 g of white solid melting at 168°-170° C. were harvested. The compound, was recrystallized from dimethylformamide to yield 2.3 g (52%) of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone oxime as a white solid, m.p.=168°-170° C. ANALYSIS: Calculated for C24H28FN3O4: 65.29%C 6.39%H 9.52%N Found: 65.27%C 6.44%H 9.46%N

Workup

  1. temperaturerefluxed for 16 hours
  2. temperaturethe mixture was cooled in an ice bath for 2 hours
  3. customThe resultant, white solid was collected
  4. washwashed with water
  5. customdried

Sources & evidence

ORD record
ord-cb8f30b604db438db388406927120e0e
Source dataset
uspto-grants-2002_06
Patent number
USRE037729E1

Reaction notes

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