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

HRID 455557Notes

Reaction equation

HRID 455557 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-44e931b605e54c7fbda8263c9fcb7c06
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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