Cyclohexylamine → Amesergide

HRID 2106720Notes

Reaction equation

HRID 2106720 reaction equation
[CH:1]([N:4]1[C:18]2[C:19]3[C:6]([CH2:7][C@@H:8]4[C@@H:13]([C:14]=3[CH:15]=[CH:16][CH:17]=2)[CH2:12][C@@H:11]([C:20](O)=[O:21])[CH2:10][N:9]4[CH3:23])=[CH:5]1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].ClC(OCC(C)C)=O.[CH:38]1([NH2:44])[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1.[OH-].[NH4+]>CN(C)C=O>[CH:38]1([NH:44][C:20]([C@@H:11]2[CH2:12][C@H:13]3[C@@H:8]([CH2:7][C:6]4[C:19]5[C:18](=[CH:17][CH:16]=[CH:15][C:14]3=5)[N:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=4)[N:9]([CH3:23])[CH2:10]2)=[O:21])[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1

Participants

7

Reactant 5

HCID 7965CyclohexylamineHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 62365Isobutyl chloroformateHCID 1825776-Methyl-1-(propan-2-yl)ergoline-8-carboxylic acid

Product 1

HCID 9821951AmesergideYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 250 ml three-neck round bottom flask was added 10.0 g (32.01 mmol) of (8β)-1-isopropyl-6-methyl ergoline-8-carboxylic acid, 4.43 g (32.1 mmol) of potassium carbonate and 200 ml of N,N-dimethylformamide. The mixture was refluxed and 25 ml of a distillate was collected. The remaining solution was cooled in an ice bath, and then with an acetonitrile/carbon dioxide bath which lowered the temperature of the reaction mixture to about -45° C. To this mixture was added 4.59 g (33.62 mmol) of isobutyl chloroformate dropwise. The resulting mixture was stirred for approximately five minutes and 3.49 g (35.21 mmol) of cyclohexylamine was added. The reaction mixture was allowed to warm to room temperature and stirred for approximately 19 hours. To the mixture was added 500 ml of ice water containing 25 ml of concentrated ammonium hydroxide. The mixture was cooled and the precipitated solid was collected by vacuum filtration. The resulting solid was washed with water and dried in vacuo to provide 10.13 g of the title compound having a purity of 92.3%. Yield 76.8%.

Workup

  1. temperatureThe mixture was refluxed
  2. distillation25 ml of a distillate was collected
  3. temperatureThe remaining solution was cooled in an ice bath
  4. customwith an acetonitrile/carbon dioxide bath which lowered
  5. customto about -45° C
  6. stirringstirred for approximately 19 hours
  7. temperatureThe mixture was cooled
  8. filtrationthe precipitated solid was collected by vacuum filtration
  9. washThe resulting solid was washed with water
  10. customdried in vacuo

Sources & evidence

ORD record
ord-a84291db7eb34318ba0321e832f43daa
Source dataset
uspto-grants-1990_06
Patent number
US04931447

Reaction notes

Loading…