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

HRID 55662

反応式

HRID 55662 の反応式
[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

参加物

4

反応物 3

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

生成物 1

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

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-313192314efe4de88312516f161f5d2d
出典データセット
uspto-grants-1997_04
特許番号
US05624927

関連ノート

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