Hydrochloric Acid → (5-Bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-hydroxypyridin-4-yl)methanone

HRID 931548ノート

反応式

HRID 931548 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C:8]([C:10]2[CH:15]=[C:14]([Cl:16])[N:13]=[C:12]([F:17])[C:11]=2[O:18]COC)=[O:9])[CH:7]=1.Cl.O.CCOC(C)=O>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:22])=[C:6]([C:8]([C:10]2[CH:15]=[C:14]([Cl:16])[N:13]=[C:12]([F:17])[C:11]=2[OH:18])=[O:9])[CH:7]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8857Ethyl AcetateHCID 86658356(5-Bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-(methoxymethoxy)pyridin-4-yl)methanone

生成物 1

HCID 86658357(5-Bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-hydroxypyridin-4-yl)methanone収率 77%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a solution of (5-bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-(methoxymethoxy)pyridin-4-yl)methanone (1200 g, 3.06 mol) in THF (4.8 L) was added 6 N aqueous HCl solution (1600 mL, 9.17 mol) and the reaction mixture was heated to 60° C. for 5 hours. The reaction mixture was cooled to RT, and then water (3 L) and EtOAc (3 L) were added. After the phases were separated, the aqueous layer was extracted with EtOAc (3 L×2). The combined organic layers was washed with brine (2 L×1) and dried over Na2SO4. The solution was concentrated under reduced pressure. The residue was dissolved in hot MTBE (700 mL). The solution was triturated with hexanes until a solid began to precipitate. The slurry was cooled to RT overnight. The solid was filtered, washed with hexanes (500 mL×2), and dried to give 821 g of (5-bromo-2-fluorophenyl)(6-chloro-2-fluoro-3-hydroxypyridin-4-yl)methanone as a yellow solid.

後処理

  1. temperatureThe reaction mixture was cooled to RT
  2. customAfter the phases were separated
  3. extractionthe aqueous layer was extracted with EtOAc (3 L×2)
  4. washThe combined organic layers was washed with brine (2 L×1)
  5. dry with materialdried over Na2SO4
  6. concentrationThe solution was concentrated under reduced pressure
  7. dissolutionThe residue was dissolved in hot MTBE (700 mL)
  8. customThe solution was triturated with hexanes until a solid
  9. customto precipitate
  10. temperatureThe slurry was cooled to RT overnight
  11. filtrationThe solid was filtered
  12. washwashed with hexanes (500 mL×2)
  13. customdried

出典と根拠

ORDレコード
ord-22c0eeee5d3e4c8db7d661dd7bf589f6
出典データセット
uspto-grants-2016_03
特許番号
US09296759B2

反応ノート

読み込み中…