Toluene → (4-Benzyl-4-hydroxypiperidin-1-yl)(2-chloropyridin-3-yl)methanone

HRID 240409ノート

反応式

HRID 240409 の反応式
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[C:11]1([CH3:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.S(Cl)(Cl)=O.CO[CH2:24][CH2:25][O:26]C>>[CH2:17]([C:25]1([OH:26])[CH2:8][CH2:9][N:10]([C:4]([C:3]2[C:2]([Cl:1])=[N:10][CH:9]=[CH:8][CH:7]=2)=[O:6])[CH2:2][CH2:24]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

参加物

5

反応物 4

HCID 1140TolueneHCID 80711,2-DimethoxyethaneHCID 24386Thionyl ChlorideHCID 762582-Chloronicotinic acid

生成物 1

HCID 86680867(4-Benzyl-4-hydroxypiperidin-1-yl)(2-chloropyridin-3-yl)methanone

反応条件

温度
90 °C

実験手順

To a mixture of 2-chloronicotinic acid (1.0 g), toluene (15 mL) and DME (5 mL) was added thionyl chloride (0.51 mL), and the mixture was stirred at 90° C. for 4 hr under a nitrogen atmosphere. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in THF (15 mL), and triethylamine (0.97 mL) and 4-benzyl-4-hydroxypiperidine (1.1 g) were added thereto. The reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere, saturated aqueous sodium hydrogen carbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.9 g).

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in THF (15 mL)
  3. additiontriethylamine (0.97 mL) and 4-benzyl-4-hydroxypiperidine (1.1 g) were added
  4. stirringThe reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere
  5. additionsaturated aqueous sodium hydrogen carbonate solution was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-e5f7df74cd774363895ee528046cda90
出典データセット
uspto-grants-2014_02
特許番号
US08648079B2

反応ノート

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