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

HRID 931582Notes

Reaction equation

HRID 931582 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([CH3:19])O.Cl.O1CCOCC1.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 866583677-bromo-3-chloro-1-fluoro-5-methyl-5H-chromeno[2,3-c]pyridin-5-ol

Product 1

HCID 866407337-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridineYield 69.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 7-bromo-3-chloro-1-fluoro-5-methyl-5H-chromeno[2,3-c]pyridin-5-ol (50 g, 145 mmol) in THF (300 mL) was added HCl in dioxane (4M, 19.95 mL, 80 mmol). The reaction was heated to 50° C. for 16 hours. The reaction was cooled to RT and K2CO3 (30.1 g, 218 mmol) was added. The reaction mixture was stirred for 30 minutes before filtering. The filtrate was concentrated under reduced pressure and the resulting crude material was washed with DCM. The solid was collected by filtration to afford 7-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridine (33.0 g, 101 mmol, 69.6% yield).

Workup

  1. temperatureThe reaction was cooled to RT
  2. filtrationbefore filtering
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. washthe resulting crude material was washed with DCM
  5. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-26b2c4b8f601489184c714be94e92680
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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