Hydrochloric Acid → HCID 13935086, compound

HRID 1164839Notes

Reaction equation

HRID 1164839 reaction equation
[C:1](O)(=O)/[CH:2]=C\C(O)=O.[CH:9]([N:12]1[C:26]2[C:27]3[C:14]([CH2:15][C@@H:16]4[C@@H:21]([C:22]=3[CH:23]=[CH:24][CH:25]=2)[CH2:20][C@@H:19]([C:28]([O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:29])[CH2:18][NH:17]4)=[CH:13]1)([CH3:11])[CH3:10].Cl>C(OCC)(=O)C>[CH:9]([N:12]1[C:26]2[C:27]3[C:14]([CH2:15][C@@H:16]4[C@@H:21]([C:22]=3[CH:23]=[CH:24][CH:25]=2)[CH2:20][C@@H:19]([C:28]([O:30][CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:29])[CH2:18][N:17]4[CH2:1][CH3:2])=[CH:13]1)([CH3:11])[CH3:10]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 13935079HCID 13935079, compound

Product 1

HCID 13935086HCID 13935086, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Two grams of 1-isopropyl-8β-cyclohexyloxycarbonylergoline maleate were converted to the free base by partitioning between 100 ml of (CH2Cl)2 and 100 ml. of saturated aqueous sodium bicarbonate. The free base passed into the organic layer. The organic layer was separated and the solvent evaporated therefrom. The resulting residue was dissolved in 15 ml of DMF, and 0.67 g of potassium carbonate and 0.75 g of ethyl iodide added to the solution. This reaction mixture was stirred at ambient temperature for about 3 days at which time HPLC indicated that starting material was no longer present. The reaction mixture was partitioned between 50 ml ethyl acetate and 50 ml of water. The organic layer was separated and the separated layer twice extracted with 50 ml portions of water. The organic layer was dried and the solvent removed by evaporation. The resulting residue (weight=1.67 g) comprising cyclohexyl 1-isopropyl-6-ethyl-8β-cyclohexyloxycarbonylergoline formed in the above reaction, was converted to the corresponding hydrochloride salt in ethyl acetate solution with gaseous HCl. Two crops of the crystalline salt were recovered by filtration; yield=1.42 g; purity by HPLC>99.2%. The crystalline fraction was slurried in a THF/ether solvent mixture and the slurry filtered. 1-Isopropyl-6-ethyl-8β-cyclohexyloxycarbonylergoline hydrochloride thus prepared melted above 220° C.; yield=1.33 g; molecular ion at 408.

Workup

  1. customby partitioning between 100 ml of (CH2Cl)2 and 100 ml
  2. customThe organic layer was separated
  3. customthe solvent evaporated
  4. dissolutionThe resulting residue was dissolved in 15 ml of DMF
  5. addition0.67 g of potassium carbonate and 0.75 g of ethyl iodide added to the solution
  6. customThe reaction mixture was partitioned between 50 ml ethyl acetate and 50 ml of water
  7. customThe organic layer was separated
  8. extractionthe separated layer twice extracted with 50 ml portions of water
  9. customThe organic layer was dried
  10. customthe solvent removed by evaporation
  11. customformed in the above reaction
  12. filtrationTwo crops of the crystalline salt were recovered by filtration
  13. filtrationthe slurry filtered
  14. custom1-Isopropyl-6-ethyl-8β-cyclohexyloxycarbonylergoline hydrochloride thus prepared
  15. custommelted above 220° C.

Sources & evidence

ORD record
ord-af96ba26b79b4077a72e7c98a6252cd1
Source dataset
uspto-grants-1990_03
Patent number
US04906639

Reaction notes

Loading…