Potassium Carbonate → 2-[4-(6-Fluoro-1,2-benzisoxazol-yl)-1-piperidinyl]-1-(2,3-dihydroindol-1-yl)ethanone fumarate

HRID 1460026Notes

Reaction equation

HRID 1460026 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+].Br[CH2:24][C:25]([N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29][CH2:28]1)=[O:26].[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]/[C:39]([OH:41])=[O:40]>C(#N)C.C(O)C.C(Cl)Cl.C(O)C>[C:36]([OH:43])(=[O:42])/[CH:37]=[CH:38]/[C:39]([OH:41])=[O:40].[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][C:25]([N:27]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[CH2:29][CH2:28]4)=[O:26])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 444972Fumaric AcidHCID 5771011-(Bromoacetyl)indolineHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 184672692-[4-(6-Fluoro-1,2-benzisoxazol-yl)-1-piperidinyl]-1-(2,3-dihydroindol-1-yl)ethanone fumarate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6342AcetonitrileSolventHCID 21584144Dichloromethane ethanolSolvent

Procedure

A stirred mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (10 g, 45.4 mmol), K2CO3 (7.2 g, 52.5 mmol) and N-(2-bromoacetyl)indoline (12 g, 50 mmol) in acetonitrile (300 ml) was heated at reflux for 4 hours. The mixture was cooled and filtered. The solution was concentrated down until solid appeared. The crystals were collected: weight 12.68 g. The mother liquor was concentrated to dryness. The residues were purified further by flash chromatography to yield an additional 1.35 g. Total yield was 14.03 g. A 2 g sample was dissolved in ethanol/methylene chloride and was treated with a solution of fumaric acid (612 mg) in ethanol to yield 2.58 g, m.p. 226°-227° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. temperatureThe mixture was cooled
  4. filtrationfiltered
  5. concentrationThe solution was concentrated down until solid
  6. customThe crystals were collected
  7. concentrationThe mother liquor was concentrated to dryness
  8. customThe residues were purified further by flash chromatography
  9. customto yield an additional 1.35 g
  10. customto yield 2.58 g, m.p. 226°-227° C.

Sources & evidence

ORD record
ord-2df6e9bcd0ad4ed3b333540e8fd41633
Source dataset
uspto-grants-1998_12
Patent number
US05854263

Reaction notes

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