Hydrochloric Acid → HCID 131718441, compound

HRID 1109182Notes

Reaction equation

HRID 1109182 reaction equation
[ClH:1].Cl.[O:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C@@H:19]3[C@@H:14]([C:15]4[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[C:16]=4[CH2:17][CH2:18]3)[CH2:13][CH2:12]2)[CH2:5][CH2:4]1.[OH-].[Na+].C(N(CC)CC)C.[CH3:34][N:35]([CH3:39])[C:36]([Cl:38])=[O:37].Cl>O.CN(C)C1C=CN=CC=1>[ClH:38].[ClH:1].[CH3:34][N:35]([CH3:39])[C:36](=[O:37])[O:24][C:20]1[C:16]2[CH2:17][CH2:18][C@H:19]3[C@H:14]([CH2:13][CH2:12][N:11]3[CH2:10][CH2:9][N:6]3[CH2:7][CH2:8][O:3][CH2:4][CH2:5]3)[C:15]=2[CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 131718437HCID 131718437, compound

Product 1

HCID 131718441HCID 131718441, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent2×

Procedure

1.00 g (0.003 mol) of rac-cis-2,3,3a,4,5,9b-hexahydro-3-(2-morpholinoethyl)-1H-benzo[e]indol-6-ol dihydrochloride dissolved in 50 ml of water was neutralized with 5.6 ml of 1N sodium hydroxide solution (5.6 mmol, 2.1 eq.). The mixture was extracted with ether, the organic phase was washed with saturated aqueous NaHCO3 and NaCl solutions, dried with Na2SO4, filtered and the filtrate was concentrated. The oily residue was dissolved in 50 ml of toluene. 0.30 g (0.41 ml, 0.003 mol) of triethylamine, 3.25 mg (266 μmol, 0.1 eq.) of 4-dimethylaminopyridine and 0.27 ml (0.003 mol) of dimethylcarbamoyl chloride were added thereto in succession. The mixture was boiled under reflux for 2 hours, poured into water and extracted with CH2Cl2. The organic phase was washed with saturated aqueous NaHCO3 and NaCl solutions, dried with Na2SO4, filtered, the filtrate was concentrated and the residue was chromatographed on 220 g of silica gel with methylene chloride/methanol (9:1). The resulting oil (0.8 g) was dissolved in 10 ml of ethanol. 0.92 ml (0.0045 mol) of 4.89N ethanolic HCl solution was added dropwise thereto and precipitation was effected with ethyl acetate. The crystals were filtered off, dissolved in hot ethanol and treated with active charcoal. After filtration, concentration and recrystallization from ethanol/ethyl acetate there was obtained 0.57 g (48%) of rac-cis-2,3,3a,4,5,9b-hexahydro-3-(2-morpholinoethyl)-1H-benzo[e]indol-6-yl dimethylcarbamate dihydrochloride as white crystals with m.p. 170°-220° (dec.).

Workup

  1. extractionThe mixture was extracted with ether
  2. washthe organic phase was washed with saturated aqueous NaHCO3 and NaCl solutions
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. dissolutionThe oily residue was dissolved in 50 ml of toluene
  7. temperatureunder reflux for 2 hours
  8. extractionextracted with CH2Cl2
  9. washThe organic phase was washed with saturated aqueous NaHCO3 and NaCl solutions
  10. dry with materialdried with Na2SO4
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated
  13. customthe residue was chromatographed on 220 g of silica gel with methylene chloride/methanol (9:1)
  14. dissolutionThe resulting oil (0.8 g) was dissolved in 10 ml of ethanol
  15. customprecipitation
  16. filtrationThe crystals were filtered off
  17. dissolutiondissolved in hot ethanol
  18. additiontreated with active charcoal
  19. filtrationAfter filtration, concentration and recrystallization from ethanol/ethyl acetate there

Sources & evidence

ORD record
ord-4eaabeb174b949d9bb7bcc811d33da4b
Source dataset
uspto-grants-1994_06
Patent number
US05318967

Reaction notes

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