Acetonitrile → 2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethoxyphtalimide hemihydrate

HRID 2184608Notes

Reaction equation

HRID 2184608 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:11]3[CH:12]=[CH:13][C:14]([F:16])=[CH:15][C:10]=3[O:9][N:8]=2)[CH2:3][CH2:2]1.BrCCO[N:21]1[C:25](=[O:26])[C:24]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]2[C:22]1=[O:31].[C:32]([O-:35])([O-])=[O:33].[K+].[K+].[C:38](#N)[CH3:39]>>[OH2:9].[F:16][C:14]1[CH:13]=[CH:12][C:11]2[C:7]([CH:4]3[CH2:3][CH2:2][N:1]([CH2:38][CH2:32][O:35][C:30]4[CH:29]=[CH:28][CH:27]=[C:24]5[C:25]([NH:21][C:22](=[O:31])[C:23]=45)=[O:26])[CH2:6][CH2:5]3)=[N:8][O:9][C:10]=2[CH:15]=1.[F:16][C:14]1[CH:13]=[CH:12][C:11]2[C:7]([CH:4]3[CH2:3][CH2:2][N:1]([CH2:39][CH2:38][O:33][C:30]4[CH:29]=[CH:28][CH:27]=[C:24]5[C:25]([NH:21][C:22](=[O:31])[C:23]=45)=[O:26])[CH2:6][CH2:5]3)=[N:8][O:9][C:10]=2[CH:15]=1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 1998751H-Isoindole-1,3(2H)-dione, 2-(2-bromoethoxy)-HCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 1317197372-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethoxyphtalimide hemihydrate

Procedure

A mixture of 3-(4-piperidinyl)-6-fluorobenzisoxazole (3.42 g, 15 mmol), N-(2-bromoethoxy)-phthalimide (4.3 g, 16 mmol) and K2CO3 (26 g, 18 mmol) in acetonitrile (150 ml) was heated at reflux for 2 hours. The solids were removed and the solvent was evaporated. The residue was purified over a flash chromatography column (packed with SiO2, 60 g: eluted with dichloromethane (DCM) and 1% CH3OH in DCM. The pure product thus obtained, weighing 6.8 g was crystallized from DCM:ethanol. Recrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate. ANALYSIS: Calculated for C22H20N3O4.0.5.H2O: 63.15%C 5.05%H 10.04%N 2.15%H2O Found: 63.20%C 5.16%H 9.80%N 2.32%H2O

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. customThe solids were removed
  4. customthe solvent was evaporated
  5. customThe residue was purified over a flash chromatography column (
  6. washeluted with dichloromethane (DCM) and 1% CH3OH in DCM
  7. customThe pure product thus obtained
  8. customwas crystallized from DCM
  9. customRecrystallization from ethanol and i-propyl ether yielded white crystals (2.4 g, m.p. 125°-127° C.) as the hemihydrate

Sources & evidence

ORD record
ord-1e430b41ba724747931ee9073fc125f8
Source dataset
uspto-grants-2002_06
Patent number
USRE037729E1

Reaction notes

Loading…