Chloroacetonitrile → 6-Fluoro-3-(1-cyanomethyl-4-piperidyl)-1,2-benzisoxazole

HRID 1900482Notes

Reaction equation

HRID 1900482 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+].Cl[CH2:24][C:25]#[N:26]>C(#N)C>[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:26])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 130783426-Fluoro-3-(1-cyanomethyl-4-piperidyl)-1,2-benzisoxazole

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (11 g, 50 mmol), K2CO3 (8.5 g, 61.6 mmol) and 2-chloroacetonitrile (5.5 g, 73 mmol) in acetonitrile (250 ml) was heated at reflux for 24 hours. The insolubles were filtered off and rinsed with methylene chloride (DCM). During concentration of the solvents on the rotary evaporator, crystals appeared. The crystals were collected and weighed 5.79 g. The product in the mother liquor was further purified by flash chromatography over a silica gel column (SiO2, 70 g; eluted with DCM, and 1% CH3OH in DCM). The second crop of product thus obtained weighed 5.2 g. The total yield was 10.9 g. The sample was recrystallized once more form ethanol, m.p. 130°-132° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 24 hours
  3. filtrationThe insolubles were filtered off
  4. washrinsed with methylene chloride (DCM)
  5. customDuring concentration of the solvents on the rotary evaporator, crystals
  6. customThe crystals were collected
  7. customThe product in the mother liquor was further purified by flash chromatography over a silica gel column (SiO2, 70 g; eluted with DCM, and 1% CH3OH in DCM)
  8. customThe second crop of product thus obtained
  9. customThe sample was recrystallized once more form ethanol, m.p. 130°-132° C.

Sources & evidence

ORD record
ord-8c7d792b0c4d4be18bec5ad7f76e3d77
Source dataset
uspto-grants-1996_11
Patent number
US05574032

Reaction notes

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