Iodine → 7-Bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,2'-oxirane]

HRID 931583Notes

Reaction equation

HRID 931583 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=[CH2:18].O.II.C([O-])([O-])=[O:23].[K+].[K+]>C1COCC1.CCOC(C)=O.[Ag]=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]3([CH2:18][O:23]3)[C:6]3[CH:11]=[C:10]([Cl:12])[N:9]=[C:8]([F:13])[C:7]=3[O:14][C:15]2=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 807IodineHCID 962WaterHCID 11430Potassium CarbonateHCID 866407337-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridine

Product 1

HCID 866583687-Bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,2'-oxirane]Yield 68.1%

Reagents, catalysts & solvents 3

HCID 92152Silver(II) oxideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-bromo-3-chloro-1-fluoro-5-methylene-5H-chromeno[2,3-c]pyridine (33 g, 101 mmol) in THF (450 mL) were added successively water (69.2 mL), iodine (51.3 g, 202 mmol) and silver(II) oxide (46.8 g, 202 mmol) at RT. The reaction mixture was stirred at RT for 10 minutes before adding K2CO3 (41.9 g, 303 mmol). After 30 minutes, the reaction mixture was diluted with EtOAc and filtered through a pad of celite. The filter cake was washed with additional EtOAc. The combined filtrate was concentrated under reduced pressure upon which a white solid precipitated. The solid was filtered off. The filtrate was further concentrated under reduced pressure to obtain a residue which was triturated with ether to afford a white precipitate. The solid was filtered off, combined with the first solid and dried under reduced pressure to afford 7-bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,2′-oxirane] (23.56 g, 68.8 mmol).

Workup

  1. waitAfter 30 minutes
  2. filtrationfiltered through a pad of celite
  3. washThe filter cake was washed with additional EtOAc
  4. concentrationThe combined filtrate was concentrated under reduced pressure upon which a white solid
  5. customprecipitated
  6. filtrationThe solid was filtered off
  7. concentrationThe filtrate was further concentrated under reduced pressure
  8. customto obtain a residue which
  9. customwas triturated with ether
  10. customto afford a white precipitate
  11. filtrationThe solid was filtered off
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-80ba3c9fa5da4eadb5c1bea9fc3399e6
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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