3-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole → 4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propoxy]-3-methoxyphenyl methanone

HRID 1899341Notes

Reaction equation

HRID 1899341 reaction equation
[O:1]1[CH2:15][CH:2]1[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[O:12])=[CH:7][C:6]=1[O:13][CH3:14].[F:16][C:17]1[CH:31]=[CH:30][C:20]2[C:21]([CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)=[N:22][O:23][C:19]=2[CH:18]=1>C(O)(C)C>[F:16][C:17]1[CH:31]=[CH:30][C:20]2[C:21]([CH:24]3[CH2:25][CH2:26][N:27]([CH2:15][CH:2]([OH:1])[CH2:3][O:4][C:5]4[CH:10]=[CH:9][C:8]([CH:11]=[O:12])=[CH:7][C:6]=4[O:13][CH3:14])[CH2:28][CH2:29]3)=[N:22][O:23][C:19]=2[CH:18]=1

Participants

4

Reactant 2

HCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 113447983-Methoxy-4-(2-oxiranylmethoxy)benzaldehyde

Product 1

HCID 184673684-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propoxy]-3-methoxyphenyl methanoneYield 89.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A stirred mixture of 4-(2,3-epoxypropoxy)-3-methoxyphenyl methanone (4.5 g, 22.5 mmol) and 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (5.36 g, 24.3 mmol) in isopropyl alcohol (150 ml) was heated at 55°0 C. for 16 hours. The mixture was cooled and the solvent was removed on a rotary evaporator. The residue was purified by flash chromatography over a silica gel column (SiO2, 80 g; eluted with dichloromethane, DCM, and 1% CH3OH in DCM). The oil thus obtained solidified quickly, weight: 9.47 g. Recrystallization from ethanol and isopropyl ether, then toluene provided 8.6 g (86%) of white crystals, m.p.=107°-108° C.

Workup

  1. temperaturewas heated at 55°0 C
  2. temperatureThe mixture was cooled
  3. customthe solvent was removed on a rotary evaporator
  4. customThe residue was purified by flash chromatography over a silica gel column (SiO2, 80 g; eluted with dichloromethane, DCM, and 1% CH3OH in DCM)
  5. customThe oil thus obtained
  6. customRecrystallization from ethanol and isopropyl ether

Sources & evidence

ORD record
ord-2634afbe003144a68850fa429a9fac28
Source dataset
uspto-grants-1996_11
Patent number
US05571803

Reaction notes

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