Tetrahydrofuran → 6-Fluoro-3-[1-(3-hydroxy-3-ethylpentyl)4-piperidinyl]-1,2-benzisoxazole
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]=1Participants
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, 3.0 M in ether) at room temperature under nitrogen (mild exotherm). The reaction mixture was for 17 hours at which time it was carefully quenched with NH4Cl (sat., 20 ml). The precipated salts were dissolved into water (25 ml) and the layers were seperated. 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
- customwas carefully quenched with NH4Cl (sat., 20 ml)
- dissolutionThe precipated salts were dissolved into water (25 ml)
- customthe layers were seperated
- extractionThe aqueous phase was extracted with EtOAc (2×)
- washthe combined organics were washed with brine
- dry with materialdried (Na2SO4)
- filtrationFiltration and concentration
- customgave the crude product which
- customwas purified via flash column chromatography (silica gel, 1% MeOH/DCM)
Sources & evidence
- ORD record
- ord-2711d9bb38724f02b237074787076a7a
- Source dataset
- uspto-grants-2000_03
- Patent number
- US06043240
Reaction notes
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