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

HRID 1899570Notes

Reaction equation

HRID 1899570 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]([NH2:27])=[O: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]([NH2:27])=[O:26])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 696322-BromoacetamideHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 184673072-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]acetamideYield 33.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (6.77 g, 30.7 mmol), K2CO3 (5 g, 36.2 mmol) and 2-bromoacetamide (4.46 g, 32.3 mmol) in acetonitrile (250 ml) was heated to reflux for 4 hours. The insolubles were filtered and rinsed with dichloromethane (DCM). The solvents were removed. The residual solid was dissolved in DCM and upon concentration of this solution, 2.3 g of product crystallized out and was collected when the volume was reduced to about 50 ml. The rest of the product in DCM was purified by flash chromatography over a silica gel column (80 gm, SiO2 ; eluted with DCM and 1% CH3OH in DCM). The total product (4.2 g) thus purified was recrystallized from ethanol to yield 2.82 g of white crystals, m.p. 170°-172° C. dec.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 hours
  3. filtrationThe insolubles were filtered
  4. washrinsed with dichloromethane (DCM)
  5. customThe solvents were removed
  6. dissolutionThe residual solid was dissolved in DCM and upon concentration of this solution, 2.3 g of product
  7. customcrystallized out and
  8. customwas collected when the volume
  9. customThe rest of the product in DCM was purified by flash chromatography over a silica gel column (80 gm, SiO2 ; eluted with DCM and 1% CH3OH in DCM)
  10. customThe total product (4.2 g) thus purified
  11. customwas recrystallized from ethanol

Sources & evidence

ORD record
ord-e017c2fe03a046a8acfccdee6ef277ef
Source dataset
uspto-grants-1996_11
Patent number
US05571828

Reaction notes

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