Tetrahydrofuran → 6-Fluoro3-[1-(3-hydroxy-3-propylhexyl)-4-piperidinyl]-1,2-benzisoxazole hydrochloride

HRID 1601581Notes

Reaction equation

HRID 1601581 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].[CH2:29]1[CH2:33]OC[CH2:30]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])([CH2:30][CH2:29][CH3:33])[CH2:24][CH2:25][CH3:26])[CH2:13][CH2:14]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 178455855HCID 178455855, compound

Product 1

HCID 184673536-Fluoro3-[1-(3-hydroxy-3-propylhexyl)-4-piperidinyl]-1,2-benzisoxazole hydrochlorideYield 45%

Procedure

To a solution of ethyl 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propionate (4.5 g, 14.0 mmol) in THF (120 ml) was added propylmagnesium 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 (2×). 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

  1. customwas carefully quenched with NH4Cl (sat., 30 ml)
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (2×)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationFiltration and concentration
  7. customgave the crude product which
  8. customwas purified via flash column chromatography (silica gel, 2% Et3N/ether)
  9. customAfter flushing the product through alumina with ether

Sources & evidence

ORD record
ord-933a19128e994d6a9398b8eefd50be4b
Source dataset
uspto-grants-1999_11
Patent number
US05977140

Reaction notes

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