Hydrochloric Acid → HCID 66611400, compound

HRID 1916432Notes

Reaction equation

HRID 1916432 reaction equation
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[C:5](=[O:16])O[C:3]=1[C:17]([OH:19])=[O:18].[CH2:20]([NH2:23])[CH2:21][CH3:22].Cl>CCO.O.S(=O)(=O)(O)O>[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[C:5](=[O:16])[N:23]([CH2:20][CH2:21][CH3:22])[C:3]=1[C:17]([OH:19])=[O:18]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 7852PropylamineHCID 66611532HCID 66611532, compound

Product 1

HCID 66611400HCID 66611400, compoundYield 89%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent3×HCID 962WaterSolvent2×HCID 1118Sulfuric AcidSolvent

Procedure

A solution of 350 mg (1.3 mmol) 4-methyl-1-oxo-7-(trifluoromethyl)-1H-isochromene-3-carboxylic acid in EtOH (15 ml) was cooled to 0° C. and treated dropwise with a solution of 1.1 ml (12.9 mmol) n-propylamine in EtOH (2 ml) at this temperature. The RS was then stirred at RT for 2 h followed by concentration in vacuo. The residue obtained was diluted with water and acidified with 2M hydrochloric acid to pH˜2 while cooling (ice-water-bath). Afterwards the RS was extracted with a MeOH/EtOAc mixture (1:9 v/v, 100 ml). The organic layer was washed with water (30 ml) and brine (20 ml), dried over Na2SO4 and concentrated in vacuo. This residue obtained was diluted with EtOH (15 ml) and 1 ml conc. sulfuric acid was added slowly at 0° C. The RS was the heated at 80° C. for 2 h. After cooling to RT, the RS was concentrated in vacuo. The residue obtained was diluted with water and extracted with a MeOH/EtOAc mixture (1:9 v/v, 100 ml). The organic layer was washed with water (30 ml) and brine (20 ml), dried over Na2SO4 and concentrated in vacuo to give 360 mg (1.1 mmo, 89%) 4-methyl-1-oxo-2-propyl-7-(trifluoromethyl)-1,2-dihydroisoquinoline-3-carboxylic acid, which was used in the next step without further purification.

Workup

  1. concentrationfollowed by concentration in vacuo
  2. customThe residue obtained
  3. extractionAfterwards the RS was extracted with a MeOH/EtOAc mixture (1:9 v/v, 100 ml)
  4. washThe organic layer was washed with water (30 ml) and brine (20 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThis residue obtained
  8. additionwas added slowly at 0° C
  9. temperatureheated at 80° C. for 2 h
  10. temperatureAfter cooling to RT
  11. concentrationthe RS was concentrated in vacuo
  12. customThe residue obtained
  13. extractionextracted with a MeOH/EtOAc mixture (1:9 v/v, 100 ml)
  14. washThe organic layer was washed with water (30 ml) and brine (20 ml)
  15. dry with materialdried over Na2SO4
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5cac4cd3234b4422b9aa10bbd042486c
Source dataset
uspto-grants-2013_12
Patent number
US08618129B2

Reaction notes

Loading…