Chloroacetyl chloride → 1-(2-Chloroacetyl)4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine

HRID 1451021Notes

Reaction equation

HRID 1451021 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(N(CC)CC)C.[Cl:24][CH2:25][C:26](Cl)=[O:27]>C(Cl)(Cl)Cl.ClCCl>[Cl:24][CH2:25][C:26]([N:12]1[CH2:11][CH2:10][CH:9]([C:6]2[C:5]3[CH:15]=[CH:16][C:2]([F:1])=[CH:3][C:4]=3[O:8][N:7]=2)[CH2:14][CH2:13]1)=[O:27]

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 184673491-(2-Chloroacetyl)4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidineYield 37.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (4.4 g, 20 mmol), triethylamine (2.1 g, 21 mmol) in chloroform (50 ml) was added to a solution of chloroacetyl chloride (2.5 g, 22 mmol) in chloroform (100 ml) dropwise at room temperature. The mixture was stirred for 2 hours. The solution was diluted with dichloromethane (DCM, 100 ml).and then washed with H2O and brine. The solvent was removed and the oily product was purified by flash chromatography (SiO2, 50 g; eluted with DCM and 1% CH3OH in DCM). The pure product was obtained as an oil, 4.2 g. Crystallization from ethanol yielded 2.2 g of white crystals, m.p. 101°-102° C.

Workup

  1. washwashed with H2O and brine
  2. customThe solvent was removed
  3. customthe oily product was purified by flash chromatography (SiO2, 50 g; eluted with DCM and 1% CH3OH in DCM)
  4. customThe pure product was obtained as an oil, 4.2 g
  5. customCrystallization from ethanol

Sources & evidence

ORD record
ord-7e7ba2ebd53043368c3649f7b3c62b64
Source dataset
uspto-grants-1997_02
Patent number
US05602158

Reaction notes

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