Pyridine → 4-(5-Chloro-2-methoxybenzamidomethyl)-6-sulfamoyl-7-methoxychroman

HRID 2394457Notes

Reaction equation

HRID 2394457 reaction equation
Cl.[NH2:2][CH2:3][CH:4]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[O:7][CH2:6][CH2:5]1.[CH3:16][O:17][C:18]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:19]=1[C:20](Cl)=[O:21].Cl[S:29]([OH:32])(=O)=[O:30].[N:33]1C=CC=CC=1>>[Cl:27][C:24]1[CH:25]=[CH:26][C:18]([O:17][CH3:16])=[C:19]([CH:23]=1)[C:20]([NH:2][CH2:3][CH:4]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[C:11]([S:29](=[O:32])(=[O:30])[NH2:33])[CH:12]=2)[O:7][CH2:6][CH2:5]1)=[O:21]

Participants

5

Reactant 4

HCID 1049PyridineHCID 24638Chlorosulfonic acid2×HCID 123841765-Chloro-2-methoxybenzoyl chlorideHCID 189736044-Aminomethyl-7-methoxychroman hydrochloride

Product 1

HCID 110484644-(5-Chloro-2-methoxybenzamidomethyl)-6-sulfamoyl-7-methoxychroman

Conditions

Temperature
60 °C

Procedure

14.8 g (64.4 mmol) of 4-aminomethyl-7-methoxychroman hydrochloride are dissolved in 75 ml of pyridine and treated with cooling to 0° C. with 13.4 g of 2-methoxy-5-chlorobenzoyl chloride. The mixture is stirred for 1.5 hours at room temperature and for 1 hour at 60° C. The cooled reaction mixture is partitioned between water and methylene chloride. The aqueous phase is extracted three times with methylene chloride. The combined organic phases are washed with 2N hydrochloric acid, water and bicarbonate solution. After drying and evaporating the organic phase, an oil is obtained. 20 g of this oil are cooled to -20° C. 30 ml of precooled chlorosulfonic acid are added with stirring. The mixture is allowed to come to room temperature with shaking and a further 5 ml of chlorosulfonic acid are added. After stirring into ice water, the precipitate obtained is filtered off with suction and, after washing with a little cold water, introduced into a solution of 200 ml of acetone and 120 ml of concentrated ammonia cooled to -20° C. The mixture is allowed to warm to room temperature, and after standing overnight the solution is concentrated in vacuo. The residue is treated with concentrated hydrochloric acid with ice cooling. The precipitate obtained is filtered off with suction and recrystallized from glacial acetic acid/methanol. 4-(5-Chloro-2-methoxybenzamidomethyl)-6-sulfamoyl-7-methoxychroman is obtained in the form of colorless crystals of melting point 202° C.

Workup

  1. additiontreated
  2. customThe cooled reaction mixture
  3. customis partitioned between water and methylene chloride
  4. extractionThe aqueous phase is extracted three times with methylene chloride
  5. washThe combined organic phases are washed with 2N hydrochloric acid, water and bicarbonate solution
  6. customAfter drying
  7. customevaporating the organic phase
  8. customan oil is obtained
  9. stirringwith stirring
  10. customto come to room temperature
  11. stirringwith shaking
  12. customthe precipitate obtained
  13. filtrationis filtered off with suction
  14. washafter washing with a little cold water
  15. additionintroduced into a solution of 200 ml of acetone and 120 ml of concentrated ammonia
  16. temperaturecooled to -20° C
  17. temperatureto warm to room temperature
  18. waitafter standing overnight
  19. concentrationthe solution is concentrated in vacuo
  20. additionThe residue is treated with concentrated hydrochloric acid with ice cooling
  21. customThe precipitate obtained
  22. filtrationis filtered off with suction
  23. customrecrystallized from glacial acetic acid/methanol

Sources & evidence

ORD record
ord-135f00509f154827bd659a929ff7762f
Source dataset
uspto-grants-1998_09
Patent number
US05811448

Reaction notes

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