Hydrochloric Acid → HCID 69743072, compound

HRID 896447Notes

Reaction equation

HRID 896447 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][C@@H:10]([CH2:15][N:16](C(OCC1C=CC=CC=1)=O)[CH2:17][CH2:18][CH2:19][CH2:20][N:21]1[C:25](=[O:26])[C:24]3[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=3[S:22]1(=[O:32])=[O:31])[CH2:9][CH2:8]2)(=O)C.[ClH:43]>[Pd].C(O)(=O)C>[ClH:43].[OH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][C@@H:10]([CH2:15][NH:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]1[C:25](=[O:26])[C:24]3[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=3[S:22]1(=[O:32])=[O:31])[CH2:9][CH2:8]2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 12085345HCID 12085345, compound

Product 1

HCID 69743072HCID 69743072, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

2 g of 10% palladium on carbon are added to 11.2 g (19 mmol) of (2R)-2-({[(benzyloxy)carbonyl][4-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-butyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl acetate in 200 ml of glacial acetic acid and 67 ml of concentrated hydrochloric acid, and the mixture is hydrogenated at 3 bar and room temperature for 4 hours. The catalyst is filtered off, and 5 ml of 25% strength aqueous ammonia are then added and the mixture is concentrated. The residue is purified by chromatography (silica gel, mobile phase dichloromethane/ethanol, gradient 1:0 to 5:1). The resulting product fractions are freed from the solvent by concentration and taken up in ethanol, and 10 ml of a 4 N solution of HCl gas in ethanol are added carefully. After cooling in ice, the resulting solid is filtered off with suction, dissolved in 550 ml of hot ethanol and treated with activated carbon. After filtration, the mixture is concentrated to about 100 ml. The precipitated crystals are filtered off with suction and dried under reduced pressure. This give 3.15 g (37% of theory) of 2-[4-({[(2R)-6-hydroxy-3,4-dihydro-2H-chromen-2-yl]methyl}amino)butyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide hydrochloride as colorless crystals.

Workup

  1. filtrationThe catalyst is filtered off
  2. addition5 ml of 25% strength aqueous ammonia are then added
  3. concentrationthe mixture is concentrated
  4. customThe residue is purified by chromatography (silica gel, mobile phase dichloromethane/ethanol, gradient 1:0 to 5:1)
  5. concentrationThe resulting product fractions are freed from the solvent by concentration
  6. addition10 ml of a 4 N solution of HCl gas in ethanol are added carefully
  7. temperatureAfter cooling in ice
  8. filtrationthe resulting solid is filtered off with suction
  9. dissolutiondissolved in 550 ml of hot ethanol
  10. additiontreated with activated carbon
  11. filtrationAfter filtration
  12. concentrationthe mixture is concentrated to about 100 ml
  13. filtrationThe precipitated crystals are filtered off with suction
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-b19bac50a23a40e08e6c169753f0b602
Source dataset
uspto-grants-2005_07
Patent number
US06919360B2

Reaction notes

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