Pyridine → 8-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 1270101Notes

Reaction equation

HRID 1270101 reaction equation
Cl.[Br:2][C:3]1[C:12]2[O:11][C:10]([CH3:14])([CH3:13])[CH2:9][NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.N1C=CC=CC=1.[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[S:28](Cl)(=[O:30])=[O:29]>C(Cl)Cl.Cl>[Br:2][C:3]1[C:12]2[O:11][C:10]([CH3:14])([CH3:13])[CH2:9][N:8]([S:28]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[F:21])(=[O:30])=[O:29])[C:7]=2[CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 1377612-Fluorobenzenesulphonyl chlorideHCID 184490998-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine hydrochloride

Product 1

HCID 225572828-bromo-4-(2-fluorobenzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazineYield 71,214.898%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

8-Bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine hydrochloride (518 mg, 2.14 mmol) was dissolved in 5 ml methylene chloride, to which pyridine (253.85 g, 3.21 mmol) was then added. The reaction mix was stirred at room temperature, and 2-fluorobenzenesulfonyl chloride (416.37 mg, 2.14 mmol) was added drop-wise to the reaction mix, after which stirring at room temperature was continued for 2 hours. The reaction mix was then heated to reflux for 1 hour, and cooled to room temperature. The reaction mix was diluted with 5 ml of methylene chloride and 10% aqueous HCl was added. The organic layer was separated, washed with water, then saturated NaHCO3, and dried (Na2SO4). Solvent was removed under reduced pressure, and the residue was purified via flash chromatography (EtOAc in hexane, 5% to 20%) to afford 610 g (71.3%) of 8-bromo-4-(2-fluoro-benzenesulfonyl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazine as an oil which solidified upon standing. MP: 108.0–110.1° C. MS: (M+H) 401.

Workup

  1. additionwas then added
  2. additionThe reaction mix
  3. additionmix
  4. stirringafter which stirring at room temperature
  5. additionThe reaction mix
  6. temperaturewas then heated
  7. temperatureto reflux for 1 hour
  8. temperaturecooled to room temperature
  9. additionThe reaction mix
  10. additionwas added
  11. customThe organic layer was separated
  12. washwashed with water
  13. dry with materialsaturated NaHCO3, and dried (Na2SO4)
  14. customSolvent was removed under reduced pressure
  15. customthe residue was purified via flash chromatography (EtOAc in hexane, 5% to 20%)

Sources & evidence

ORD record
ord-d936c3d72ff44970bc78b4df1aba9344
Source dataset
uspto-grants-2007_04
Patent number
US07202241B2

Reaction notes

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