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

HRID 335796Notes

Reaction equation

HRID 335796 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]Cl>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

4

Reactant 2

HCID 574756427-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-oneHCID 178418332HCID 178418332, compound2×

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-one (50 mg, 0.152 mmol) in 5 mL of dry THF at −78 C was added methylmagnesium chloride, 3.0 m solution in tetrahydrofuran (16.87 μL, 0.228 mmol) (0.07 mL) and the reaction was slowly warmed up to −30 C. Only half of conversion was detected. To this was added another batch of methylmagnesium chloride, 3.0 m solution in THF (16.87 μL, 0.228 mmol) (0.07 mL). The reaction was quenched at −30 C with sat. NH4Cl, extracted with EA, dried over Na2SO4, filtered and evaporated to dryness. It was then treated with 1 mg of PPTS in DCM at 25 C for 0.5 h. After cooling, 0.1 g of NaHCO3 was added the solvent was evaporated to dryness to give crude 7-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridine which was directly used in the next step.

Workup

  1. temperaturethe reaction was slowly warmed up to −30 C
  2. customThe reaction was quenched at −30 C with sat. NH4Cl
  3. extractionextracted with EA
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. additionIt was then treated with 1 mg of PPTS in DCM at 25 C for 0.5 h
  8. temperatureAfter cooling
  9. addition0.1 g of NaHCO3 was added the solvent
  10. customwas evaporated to dryness

Sources & evidence

ORD record
ord-14de138589464d958327857e04a8a847
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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