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

HRID 977780Notes

Reaction equation

HRID 977780 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-6a23410fbc7b4242aa026098aa99425f
Source dataset
uspto-grants-1997_03
Patent number
US05614543

Reaction notes

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