Ethyl Acetate → HCID 70981527, compound

HRID 879343Notes

Reaction equation

HRID 879343 reaction equation
[Br:1][C:2]1[S:3][C:4]2[C:10](=[O:11])[CH2:9][CH:8]([CH3:12])[CH2:7][C:5]=2[N:6]=1.BrBr.N12CCCN=C1CCCCC2.CCOC(C)=O>C(O)(=O)C.ClCCl>[Br:1][C:2]1[S:3][C:4]2[C:10]([OH:11])=[CH:9][C:8]([CH3:12])=[CH:7][C:5]=2[N:6]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24408BromineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 70982538HCID 70982538, compound

Product 1

HCID 70981527HCID 70981527, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-bromo-5-methyl-5,6-dihydrobenzo[d]thiazol-7(4H)-one (17.5 g, 71.24 mmol) in acetic acid (142 mL) at 80° C. was added dropwise bromine (3.30 mL, 64.12 mmol) over 30 minutes. Reaction mixture was stirred for 1 h at 80° C., cooled to room temperature and resulting solid collected by filtration. The filter cake was partitioned between dichloromethane/saturated sodium bicarbonate solution. The organic layer was washed with saturated sodium bicarbonate solution, brine, dried (MgSO4), filtered and concentrated. The residue was dissolved in dichloromethane (250 mL) and added dropwise over 2.5 h to a solution of 1,8-Diazabicyclo[5.4.0]undec-7-ene (19.5 mL, 130 mmol) in dichloromethane (1.5 L) at 0° C. Reaction mixture was stirred for 30 minutes, quenched with 1N HCl and stirred for 5 minutes. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. Purification by CombiFlash (220 g, 5 to 40% EtOAc/Hex) gave impure product. Recystallization from hot EtOAc/Hex gave pure product. NMR (400 MHz, CDCl3): δ 7.42 (s, 1H), 6.65 (s, 1H), 2.44 (s, 3H).

Workup

  1. customReaction mixture
  2. temperaturecooled to room temperature
  3. customresulting solid
  4. filtrationcollected by filtration
  5. customThe filter cake was partitioned between dichloromethane/saturated sodium bicarbonate solution
  6. washThe organic layer was washed with saturated sodium bicarbonate solution, brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in dichloromethane (250 mL)
  11. customReaction mixture
  12. stirringwas stirred for 30 minutes
  13. customquenched with 1N HCl
  14. stirringstirred for 5 minutes
  15. washThe organic layer was washed with brine
  16. dry with materialdried (MgSO4)
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customPurification by CombiFlash (220 g, 5 to 40% EtOAc/Hex)
  20. customgave impure product

Sources & evidence

ORD record
ord-8c76cee7cd364d888556ffdca3c81d35
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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