Acetonitrile → 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]-2,2,2-trifluoroethanone

HRID 2184501Notes

Reaction equation

HRID 2184501 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.Cl[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:33])[C:29]([F:32])([F:31])[F:30])=[CH:24][C:23]=1[O:34][CH3:35].C([O-])([O-])=O.[K+].[K+].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]([CH2:18][CH2:19][CH2:20][O:21][C:22]4[CH:27]=[CH:26][C:25]([C:28](=[O:33])[C:29]([F:30])([F:31])[F:32])=[CH:24][C:23]=4[O:34][CH3:35])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 100174981-[4-(3-Chloropropoxy)-3-methoxyphenyl]-2,2,2-trifluoroethanone

Product 1

HCID 104352741-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxyphenyl]-2,2,2-trifluoroethanoneYield 56%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (1.5 g, 6.7 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]-2,2,2-trifluoroethanone (2.0 g, 6.7 mmol). K2CO3 (0.88 g). Kl (0.1 g) and acetonitrile (50 ml.) was stirred and refluxed for 16 hours. After cooling, the reaction was poured into water and the aqueous mixture extracted with ethyl acetate. The extract was washed (H2O), dried (MgSO4), and the solvent was concentrated to an oil, which upon evacuation at high vacuum afforded 3.2 g of a waxy solid. The solid was chromatographed on a Waters preparative LC (silica columns, eluting with methanol-dichloromethane). Concentration of the appropriate fractions gave 1.8 g (56%) of 1-[4-[3-[4- (6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]-propoxy]-3-methoxyphenyl]-2,2,2-trifluoroethanone solid, m.p.=94°-96° C.

Workup

  1. temperaturerefluxed for 16 hours
  2. temperatureAfter cooling
  3. extractionthe aqueous mixture extracted with ethyl acetate
  4. washThe extract was washed (H2O)
  5. dry with materialdried (MgSO4)
  6. concentrationthe solvent was concentrated to an oil, which upon evacuation at high vacuum
  7. customafforded 3.2 g of a waxy solid
  8. customThe solid was chromatographed on a Waters preparative LC (silica columns, eluting with methanol-dichloromethane)

Sources & evidence

ORD record
ord-d8a185aa93b64222a8534d2f19003546
Source dataset
uspto-grants-2002_06
Patent number
USRE037729E1

Reaction notes

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