Tetrahydrofuran → 6-Fluoro-3-[1-(3-hydroxy-3-ethylpentyl)4-piperidinyl]-1,2-benzisoxazole

HRID 581561Notes

Reaction equation

HRID 581561 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17](OCC)=[O:18])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[CH2:24]([Mg]Br)[CH3:25].[CH2:28]1COC[CH2:29]1>>[F:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]([OH:18])([CH2:24][CH3:25])[CH2:28][CH3:29])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21959991Ethyl 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]propionateHCID 178418443HCID 178418443, compound

Product 1

HCID 184673426-Fluoro-3-[1-(3-hydroxy-3-ethylpentyl)4-piperidinyl]-1,2-benzisoxazoleYield 61%

Procedure

To a solution of ethyl 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propionate (3.9 g, 12.0 mmol) in THF (100 ml) was added ethylmagnesium bromide (12.0 ml, 36.0 mmol, 3.0M in ether) at room temperature under nitrogen (mild exotherm). The reaction mixture was stirred for 17 hours at which time it was carefully quenched with NH4Cl (sat., 20 ml). The precipitated salts were dissolved into water (25 ml) and the layers were separated. The aqueous phase was extracted with EtOAc (2×) and the combined organics were washed with brine and dried (Na2SO4). Filtration and concentration gave the crude product which was purified via flash column chromatography (silica gel, 1% MeOH/DCM) to give 2.4 g (61%) of the desired product as an oil which solidified on standing, m.p.=50-53° C.

Workup

  1. customwas carefully quenched with NH4Cl (sat., 20 ml)
  2. dissolutionThe precipitated salts were dissolved into water (25 ml)
  3. customthe layers were separated
  4. extractionThe aqueous phase was extracted with EtOAc (2×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationFiltration and concentration
  8. customgave the crude product which
  9. customwas purified via flash column chromatography (silica gel, 1% MeOH/DCM)

Sources & evidence

ORD record
ord-50cb9d4c14734682ba54ac766bb29e87
Source dataset
uspto-grants-1999_07
Patent number
US05919798

Reaction notes

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