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]([O:19]CC)=O)[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[CH2:24]([Mg][Cl:28])[CH2:25][CH3:26].[Cl-].[CH2:30]1[CH2:34]OC[CH2:31]1>>[ClH:28].[F:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][C:17]([OH:19])([CH2:31][CH2:30][CH3:34])[CH2:24][CH2:25][CH3:26])[CH2:13][CH2:14]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 (4.5 g, 14.0 mmoi) in THF (120 ml) was added propylmagnesium chloride (21.1 ml, 42.0 mmol, 2.0M in ethepropylmagnesium chloride (21.1 ml, 42.0 mmol, 2.0M 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., 30 ml). The layers were separated and the aqueous phase was extracted with EtOAc (2X). 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, 2% Et3N/ether). After flushing the product through alumina with ether, the hydrochloride salt was prepared in ether/EtOAc (1:1, 40 ml, 1 drop IPA) with ethereal HCl to give 2.5 g (45%) of the desired product as a white solid, m.p.=163°-164° C.
Workup
- customwas carefully quenched with NH4Cl (sat., 30 ml)
- customThe layers were separated
- extractionthe aqueous phase was extracted with EtOAc (2X)
- 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, 2% Et3N/ether)
- customAfter flushing the product through alumina with ether
Sources & evidence
- ORD record
- ord-3b0e6046c31d467e8df90f8e1f1fb6ea
- Source dataset
- uspto-grants-1997_01
- Patent number
- US05597842
Linked notes
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