Acetic Acid → 6-Chloro-4-o-tolyl-nicotinic acid

HRID 1017477

反応式

HRID 1017477 の反応式
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[C:11]1([CH3:19])[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[Mg]Cl.C(O)(=O)C>C1COCC1.O.O.C([O-])(=O)C.[Mn+3].C([O-])(=O)C.C([O-])(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH3:19])[C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 176Acetic AcidHCID 792226-Chloronicotinic acidHCID 178424304HCID 178424304、化合物

生成物 1

HCID 121673176-Chloro-4-o-tolyl-nicotinic acid収率 51%

試薬・触媒・溶媒 2

HCID 12416832Manganese triacetate dihydrate触媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

13.0 g (82.5 mMol) 6-Chloro-nicotinic acid in 65 ml THF were cooled to 0° C. and 206.3 ml (206.3 mMol) o-tolylmagnesium chloride solution (1M in THF) were added over 45 minutes. The solution obtained was further stirred 3 hours at 0° C. and overnight at room temperature. It was cooled to −60° C. and 103.8 ml (1.8 Mol) acetic acid were added, followed by 35 ml THF and 44.24 g (165 mMol) manganese(III) acetate dihydrate. After 30 minutes at −60° C. and one hour at room temperature, the reaction mixture was filtered and THF removed under reduced pressure. The residue was partitioned between water and dichloromethane and extracted. The crude product was filtered on silica gel (eluent:ethyl acetate/toluene/formic acid 20:75:5) then partitioned between 200 ml aqueous half-saturated sodium carbonate solution and 100 ml dichloromethane. The organic phase was washed with 50 ml aqueous half-saturated sodium carbonate solution. The combined aqueous phases were acidified with 25 ml aqueous HCl 25% and extracted with dichloromethane. The organic extracts were dried (Na2SO4) and concentrated under reduced pressure to yield 10.4 g (51%) of 6-chloro-4-o-tolyl-nicotinic acid as a yellow foam.

後処理

  1. customThe solution obtained
  2. temperatureIt was cooled to −60° C.
  3. waitAfter 30 minutes at −60° C.
  4. filtrationone hour at room temperature, the reaction mixture was filtered
  5. customTHF removed under reduced pressure
  6. customThe residue was partitioned between water and dichloromethane
  7. extractionextracted
  8. filtrationThe crude product was filtered on silica gel (eluent:ethyl acetate/toluene/formic acid 20:75:5)
  9. customthen partitioned between 200 ml aqueous half-saturated sodium carbonate solution and 100 ml dichloromethane
  10. washThe organic phase was washed with 50 ml aqueous half-saturated sodium carbonate solution
  11. extractionextracted with dichloromethane
  12. dry with materialThe organic extracts were dried (Na2SO4)
  13. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-2c08912cff774c09b18033f570b48593
出典データセット
uspto-grants-2002_11
特許番号
US06479483B2

関連ノート

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