Diisopropyl Ether → HCID 22865044, compound

HRID 363629Notes

Reaction equation

HRID 363629 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:17]([O-:20])([O-:19])=O.[K+].[K+].Br[CH2:24][C@H:25]([CH3:28])[CH2:26][OH:27].C(OC(C)C)(C)C>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)C.O>[C:4]([OH:27])(=[O:8])/[CH:5]=[CH:15]/[C:17]([OH:20])=[O:19].[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@@H:25]([CH3:28])[CH2:26][OH:27])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 7914Diisopropyl EtherHCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 10441885(R)-(-)-3-Bromo-2-methyl-1-propanol

Product 1

HCID 22865044HCID 22865044, compound

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (14.5 g, 65 mmol), K2CO3 (10 g, 72 mmol). (R)-(-)-3-bromo-2-methyl-1-propanol (10 g, 65.3 mmol), tetrabutylammonium hydrogen sulfate (1,27 g, phase transfer catalyst) in acetonitrile (300 ml) and H2O (5 ml) was heated at reflux for 6 hours. The mixture was cooled and the solvent was removed on rotary evaporator. The residue was extracted into methylene chloride (DCM), and the insolubles were filtered. After concentration of the extract, the crude product was purified by flash chromatography over a silica gel column (SiO2, 150 g; eluted with DCM, 11; 2% CH3OH in DCM, 1.6). The material thus purified weighed 17 g (89%). The sample for testing was prepared by treatment of a sample (2.28 g) with fumaric acid (953 mg) in ethanol. The crystals fonned slowly upon addition of isopropyl ether. These were collected and dried: weight 1.84 g, m.p.=114°-115° C.

Workup

  1. temperatureat reflux for 6 hours
  2. temperatureThe mixture was cooled
  3. customthe solvent was removed on rotary evaporator
  4. extractionThe residue was extracted into methylene chloride (DCM)
  5. filtrationthe insolubles were filtered
  6. customAfter concentration of the extract, the crude product was purified by flash chromatography over a silica gel column (SiO2, 150 g; eluted with DCM, 11; 2% CH3OH in DCM, 1.6)
  7. customThe material thus purified
  8. customThe sample for testing was prepared by treatment of a sample (2.28 g) with fumaric acid (953 mg) in ethanol
  9. customThese were collected
  10. customdried

Sources & evidence

ORD record
ord-8486c39496cf49f4826eab06e7460c1c
Source dataset
uspto-grants-1999_02
Patent number
US05874435

Reaction notes

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