Hydrochloric Acid → 7-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridine

HRID 335900Notes

Reaction equation

HRID 335900 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=[CH:16][CH:17]=1)[O:14][C:7]1[C:8]([F:13])=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]2=O.[CH3:19][Mg]Br.[Cl-].[NH4+].Cl>C1COCC1.O.C(OCC)(=O)C.C(OCC)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:15](=[CH:16][CH:17]=1)[O:14][C:7]1[C:8]([F:13])=[N:9][C:10]([Cl:12])=[CH:11][C:6]=1[C:5]2=[CH2:19]

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 25517Ammonium ChlorideHCID 574756427-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-oneHCID 178418573HCID 178418573, compound

Product 1

HCID 866407337-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridine

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

7-Bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-one (21.5 g, 65.4 mmol) was suspended in dry THF (300 mL) under nitrogen in an ice bath. Methylmagnesium bromide (3.0 M in diethyl ether, 36 mL, 108 mmol) was added in ˜12 mL portions allowing 10-15 minutes between additions. The mixture was stirred for a 15 minutes after the final addition. Saturated ammonium chloride (50 mL) was added carefully followed by diethyl ether (200 mL), ethyl aceate (200 mL), water (400 mL) and 2 N HCl (50 mL). The phases were mixed and separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. The crude alcohol was dissolved in dry THF (300 mL) and treated with HCl (4.0 M solution in 1,4-dioxane, 16 mL, 64.0 mmol). The mixture was heated to 50° C. and stirred for 30 minutes. The crude reaction mixture was evaporated to dryness under reduced pressure. The crude tar was triturated with diethyl ether (200 mL) and stirred in an ice bath. A cream coloured solid precipitated within a few minutes. After 10 minutes the mixture was filtered through a sintered glass frit and dried under high vacuum to give the desired 7-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridine.

Workup

  1. additionaddition
  2. additionThe phases were mixed
  3. customseparated
  4. dry with materialthe organic dried with magnesium sulfate
  5. custombefore evaporating to dryness under reduced pressure
  6. dissolutionThe crude alcohol was dissolved in dry THF (300 mL)
  7. stirringstirred for 30 minutes
  8. customThe crude reaction mixture
  9. customwas evaporated to dryness under reduced pressure
  10. customThe crude tar was triturated with diethyl ether (200 mL)
  11. stirringstirred in an ice bath
  12. customprecipitated within a few minutes
  13. filtrationAfter 10 minutes the mixture was filtered through a sintered glass frit
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-c8bd8acb874d47ae95f0fcc430651593
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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