Phenol → HCID 178513773, compound

HRID 1266358Notes

Reaction equation

HRID 1266358 reaction equation
[C:1]1([O:7][C:8](=[O:25])[NH:9][C:10]2[S:14][N:13]=[C:12]([O:15]CC3C=CC=CC=3)[C:11]=2[C:23]#[N:24])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1([OH:32])C=CC=CC=1>S(=O)(=O)(O)O>[C:1]1([O:7][C:8](=[O:25])[NH:9][C:10]2[S:14][N:13]=[C:12]([OH:15])[C:11]=2[C:23](=[O:32])[NH2:24])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 996PhenolHCID 29939179Phenyl (3-(benzyloxy)-4-cyanoisothiazol-5-yl)carbamate

Product 1

HCID 178513773HCID 178513773, compound

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent2×

Procedure

The wet solid, (3-Benzyloxy-4-cyano-isothiazol-5-yl)-carbamic acid phenyl ester, (320 g) was added slowly to concentrated sulfuric acid (650 mL) over 1.5 hours. Additional concentrated sulfuric acid (100 mL) was added and the mixture stirred a further 3 hours. The viscous solution was diluted by slow addition of ice (2000 g) followed by vigorous stirring for an additional 2 hours. The acid was partially removed by dividing the suspension into eight containers that were placed in a centrifuge, spun at 3000 rpm for 45 minutes at 21° C. The aqueous layer was discarded, additional pure water was added, the pellet resuspended, and the process repeated. After seven dilution/centrifugation/redilution cycles, the pH of the aqueous layer had increased to ˜4 and the solid was collected and dried by drawing air through a cake in a funnel for 2 days. The less-wet solid was crushed, placed again in the filter, and air was again drawn through the solid for another day. This process was repeated until the solid was dry to afford a tan solid (234 g, 105% over two steps, minor impurities present—did not interfere appreciably with the subsequent steps). 1H NMR (400 MHz, DMSO) δ 7.00 (broad s, 1H), 7.27-7.31 (m, 3H), 7.40-7.45 (m, 2H), 7.89 (s, 1H), 8.08 (s, 1H), 11.92 (s, 1H); MS (APCl, m/z): 184 [M-(H and PhOH)]−.

Workup

  1. stirringby vigorous stirring for an additional 2 hours
  2. customThe acid was partially removed
  3. waitspun at 3000 rpm for 45 minutes at 21° C
  4. additionadditional pure water was added
  5. temperatureAfter seven dilution/centrifugation/redilution cycles, the pH of the aqueous layer had increased to ˜4
  6. customthe solid was collected
  7. customdried
  8. customfor 2 days
  9. customThe less-wet solid was crushed
  10. waitwas again drawn through the solid for another day
  11. customwas dry
  12. customto afford a tan solid (234 g, 105% over two steps, minor impurities present—did not

Sources & evidence

ORD record
ord-5fb894abf34f456294d6d509093d9a73
Source dataset
uspto-grants-2003_04
Patent number
US06548526B2

Reaction notes

Loading…