Acetic Acid → HCID 15586938, compound

HRID 225197Notes

Reaction equation

HRID 225197 reaction equation
[C:1]([OH:4])(=O)[CH3:2].ClC(OCC(C)C)=O.CN1CCOCC1.[CH3:20][N:21]1[C:35]2[C:36]3[C:23]([CH2:24][C@@H:25]4[C@@H:30]([C:31]=3[CH:32]=[CH:33][CH:34]=2)[CH2:29][C@@H:28]([CH2:37][NH:38][NH2:39])[CH2:27][N:26]4[CH3:40])=[CH:22]1>C(#N)C>[CH3:20][N:21]1[C:35]2[C:36]3[C:23]([CH2:24][C@@H:25]4[C@@H:30]([C:31]=3[CH:32]=[CH:33][CH:34]=2)[CH2:29][C@@H:28]([CH2:37][NH:38][NH:39][C:1](=[O:4])[CH3:2])[CH2:27][N:26]4[CH3:40])=[CH:22]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 15586934HCID 15586934, compound

Product 1

HCID 15586938HCID 15586938, compoundYield 60.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
-15 °C

Procedure

0.6 g of acetic acid are dissolved in 25 ml of acetonitrile with stirring. The solution is cooled to -15° C., and 1.39 ml of isobutyl chloroformate and 1.1 ml of N-methyl-morpholine are added. After 5 minutes of stirring a solution of 2.8 g of 1,6-dimethyl-8β-hydrazinomethyl-ergoline in 10 ml of acetonitrile is added to the mixture. The mixture is slowly (within 30 minutes) warmed to room temperature, stirred at room temperature for 2 hours, then evaporated in vacuo. The residue is dissolved in 200 ml of chloroform, and 100 ml of water are added. The pH of the aqueous phase is adjusted to 8 with 10% aqueous ammonia, and the mixture is shaken. The organic phase is separated, and the aqueous phase is extracted thrice with 100 ml of chloroform. The chloroform fractions are combined and evaporated to dryness in vacuo. The residue is subjected to column chromatography in order to remove the occasional impurities. 60 g of silica gel are used as adsorbent, and the column is eluted with a 30:0.3:9 mixture of chloroform, water and methanol. The effluent is analyzed by thin layer chromatography. The fractions containing a substance with an Rf value of 0.75 are combined, evaporated in vacuo, and the residue is crystallized from alcohol. 1.9 g (60.4%) of 1,6-dimethyl-8β-[(N'-acetyl-hydrazino)-methyl]-ergoline are obtained; m.p.: 190°-192° C., [α]D20 =-29.7° (c=1, in 96% ethanol).

Workup

  1. additionis added to the mixture
  2. custom(within 30 minutes)
  3. temperaturewarmed to room temperature
  4. stirringstirred at room temperature for 2 hours
  5. customevaporated in vacuo
  6. dissolutionThe residue is dissolved in 200 ml of chloroform
  7. addition100 ml of water are added
  8. stirringthe mixture is shaken
  9. customThe organic phase is separated
  10. extractionthe aqueous phase is extracted thrice with 100 ml of chloroform
  11. customevaporated to dryness in vacuo
  12. customto remove the occasional impurities
  13. washis eluted with a 30:0.3:9 mixture of chloroform, water and methanol
  14. additionThe fractions containing a substance with an Rf value of 0.75
  15. customevaporated in vacuo
  16. customthe residue is crystallized from alcohol

Sources & evidence

ORD record
ord-ba03052c18e3495bac61fa88131029fd
Source dataset
uspto-grants-1980_11
Patent number
US04235912

Reaction notes

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