Hydrochloric Acid → 1000210-63-8

HRID 1672371Notes

Reaction equation

HRID 1672371 reaction equation
C(O)C.C(OC(=O)[NH:10][CH2:11][CH2:12][S:13]([C:16]1[C:17]2[CH:18]=[CH:19][N:20]=[CH:21][C:22]=2[CH:23]=[C:24]([C:26]2[CH:31]=[CH:30][C:29]([O:32]C3CCCCO3)=[CH:28][CH:27]=2)[CH:25]=1)(=[O:15])=[O:14])(C)(C)C.[ClH:40]>O>[ClH:40].[ClH:40].[NH2:10][CH2:11][CH2:12][S:13]([C:16]1[CH:25]=[C:24]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)[CH:23]=[C:22]2[C:17]=1[CH:18]=[CH:19][N:20]=[CH:21]2)(=[O:14])=[O:15]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 702EthanolHCID 67331493HCID 67331493, compound

Product 1

HCID 236584011000210-63-8Yield 101.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

The 60 L reactor is charged with ethanol (24 L) and (2-{7-[4-(Tetrahydro-pyran-2-yloxy)-phenyl]-isoquinoline-5-sulfonyl}-ethyl)-carbamic acid tert-butyl ester (2.652 kg; 5.173 moles). The (2-{7-[4-(Tetrahydro-pyran-2-yloxy)-phenyl]-isoquinoline-5-sulfonyl}-ethyl)-carbamic acid tert-butyl ester is rinsed in with ethanol (2.6 L). Hydrochloric acid solution (31.9%; 1780 g; 15.6 moles) is diluted with water (1.42 L). This HCl solution is charged to the reactor and rinsed in with water (0.2 L). The reaction is warmed to 70° C. A yellow solution forms around 30° C. and a yellow slurry reforms near 70° C. The reaction is held at 70° C. for ½ hr and then is warmed up to reflux (78° C.). HPLC indicates a complete reaction after 1.5 hrs at reflux. Water (14.5 L) is added to the reaction over 13 minutes. The temperature drops to 69° C. The reaction is heated back to reflux (80° C.) and a solution forms. The reaction is cooled to 68° C. and solid begins forming. The reaction is held at 68° C. for ½ hr and then cools to 2° C. over 1.5 hrs. The slurry is held at 1-2° C. for 1 hr. The solid is filtered and washed with ethanol (4.6 L). The wet cake weight is 3.236 kg. The solid is dried in vacuo at 50° C. to give 2.106 kg (101.4% of theory) 4-[5-(2-amino-ethanesulfonyl)-isoquinolin-7-yl]-phenol di-hydrochloride salt. Mass Spectrum (LCMS) m/z=402.31) (M+H).

Workup

  1. washThe (2-{7-[4-(Tetrahydro-pyran-2-yloxy)-phenyl]-isoquinoline-5-sulfonyl}-ethyl)-carbamic acid tert-butyl ester is rinsed in with ethanol (2.6 L)
  2. washrinsed in with water (0.2 L)
  3. customA yellow solution forms around 30° C.
  4. customa yellow slurry reforms near 70° C
  5. temperatureis warmed up
  6. temperatureto reflux (78° C.)
  7. customa complete reaction after 1.5 hrs
  8. temperatureat reflux
  9. customdrops to 69° C
  10. temperatureThe reaction is heated back
  11. temperatureto reflux (80° C.)
  12. temperatureThe reaction is cooled to 68° C.
  13. customsolid begins forming
  14. waitThe reaction is held at 68° C. for ½ hr
  15. waitcools to 2° C. over 1.5 hrs
  16. waitThe slurry is held at 1-2° C. for 1 hr
  17. filtrationThe solid is filtered
  18. washwashed with ethanol (4.6 L)
  19. customThe solid is dried in vacuo at 50° C.

Sources & evidence

ORD record
ord-7f546ef269ae480eaf70f1f8e87ed969
Source dataset
uspto-grants-2011_08
Patent number
US07998977B2

Reaction notes

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