Ethanol → 1000210-64-9

HRID 1672369Notes

Reaction equation

HRID 1672369 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][S:10]([C:13]1[C:14]2[CH:15]=[CH:16][N:17]=[CH:18][C:19]=2[CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([O:29]C)=[CH:25][CH:24]=2)[CH:22]=1)(=[O:12])=[O:11])(C)(C)C.B(Br)(Br)Br.C(O)C>ClCCl>[NH2:7][CH2:8][CH2:9][S:10]([C:13]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][N:17]=[CH:18]2)(=[O:11])=[O:12]

Participants

5

Reactant 3

HCID 702EthanolHCID 25134Boron tribromideHCID 67331428HCID 67331428, compound

Product 1

HCID 236358031000210-64-9Yield 55.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To {2-[7-(4-methoxy-phenyl)-isoquinoline-5-sulfonyl]-ethyl}-carbamic acid tert-butyl ester (25.00 g, 56.49 mmol) in dichloromethane (1 L) at 0° C. add BBr3 (1.0 M in dichloromethane, 200 mL, 200 mmol) over 40 min with vigorous overhead stirring. Remove the cooling bath and stir at room temperature overnight. Cool to 0° C. and add methanol (500 mL) dropwise over 1 h. Filter the resulting slurry, rinse the flask with dichloromethane (100 mL) and wash the solids with the rinse. Wash the solids with additional dichloromethane (150 mL) and dry under vacuum filtration. Slurry the solids in methanol (400 mL) with stirring, then concentrate under vacuum to a thin paste. Add additional methanol (400 mL) and further slurry the solids with stirring. Concentrate the slurry under vacuum to dryness, and dry the solids overnight under vacuum. Pulverize the solids to a powder and slurry in methanol (1 L). Add Amberlyst® A-21 resin (75 g) and stir until the powder is dissolved. Filter the resin, slurry the filtered resin in methanol (220 mL) and filter the resin again, combining the filtrates. Wash the filtered resin with methanol (100 mL) and add this wash to the filtrates. Combine the filtrates with ethanol (200 mL) and concentrate the mixture under vacuum to a volume of about 200 mL to afford a slurry. Add ethanol (400 mL), warm the slurry to 50° C. for about 15 min, then concentrate under vacuum to a volume of about 200 mL. Cool the slurry to room temperature, filter and rinse the filter cake with ethanol (2×15 mL), then dry under vacuum to afford the title compound (10.22 g, 55%) as a tan solid. Mass spectrum (LCMS) m/z=329.0 (M+H+).

Workup

  1. customRemove the cooling bath
  2. stirringstir at room temperature overnight
  3. additionadd methanol (500 mL) dropwise over 1 h
  4. filtrationFilter the resulting slurry
  5. washrinse the flask with dichloromethane (100 mL)
  6. washwash the solids with the rinse
  7. washWash the solids with additional dichloromethane (150 mL)
  8. customdry under vacuum filtration
  9. stirringwith stirring
  10. concentrationconcentrate under vacuum to a thin paste
  11. additionAdd additional methanol (400 mL) and further slurry the solids
  12. stirringwith stirring
  13. concentrationConcentrate the slurry under vacuum to dryness
  14. customdry the solids overnight under vacuum
  15. stirringAdd Amberlyst® A-21 resin (75 g) and stir until the powder
  16. dissolutionis dissolved
  17. filtrationFilter the resin
  18. filtrationfilter the resin again
  19. washWash the filtered resin with methanol (100 mL)
  20. additionadd
  21. washthis wash to the filtrates
  22. concentrationCombine the filtrates with ethanol (200 mL) and concentrate the mixture under vacuum to a volume of about 200 mL
  23. customto afford a slurry
  24. concentrationconcentrate under vacuum to a volume of about 200 mL
  25. temperatureCool the slurry to room temperature
  26. filtrationfilter
  27. washrinse the filter cake with ethanol (2×15 mL)
  28. customdry under vacuum

Sources & evidence

ORD record
ord-5ff8620f6162407eac79c924403edaa7
Source dataset
uspto-grants-2011_08
Patent number
US07998977B2

Reaction notes

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