Ethyl Bromide → Vinpocetine

HRID 258813

Reaction equation

HRID 258813 reaction equation
[CH3:1][CH2:2][C@:3]12[CH:21]=[C:20]([C:22]([OH:24])=[O:23])[N:19]3[C:9]4=[C:10]([C:13]5[C:18]3=[CH:17][CH:16]=[CH:15][CH:14]=5)[CH2:11][CH2:12][N:7]([C@@H:8]14)[CH2:6][CH2:5][CH2:4]2.[OH-].[K+].[CH2:27](Br)[CH3:28]>C(O)C>[CH3:1][CH2:2][C@:3]12[CH:21]=[C:20]([C:22]([O:24][CH2:27][CH3:28])=[O:23])[N:19]3[C:9]4=[C:10]([C:13]5[C:18]3=[CH:17][CH:16]=[CH:15][CH:14]=5)[CH2:11][CH2:12][N:7]([C@@H:8]14)[CH2:6][CH2:5][CH2:4]2

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 14797Potassium HydroxideHCID 160154(+)-Apovincaminic acid

Product 1

HCID 443955VinpocetineYield 66%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1 g. (0.0031 moles) of apovincaminic acid and 0.17 g. (0.003 moles) of potassium hydroxide are dissolved in 80 ml. of anhydrous ethanol, thereafter 0.4 g. (0.0036 moles) of ethyl bromide are added to the solution. The solution is boiled under reflux for 3 hours. The reaction is monitored by layer chromatography. The solution is cooled and evaporated to dryness under reduced pressure. The dry residue is dissolved in 500 ml. of 2% aqueous sulfuric acid, and the solution is filtered. The pH of the filtrate is adjusted to 8 with 5% aqueous sodium hyrodxide solution. A small amount of precipitate separates. The mixture is extracted with 200 ml. portions of methylene chloride until no positive Mayer reaction can be observed in the aqueous phase. The organic phases are separated, combined, dried over anhydrous potassium carbonate, filtered and evaporated to dryness under reduced pressure. The dry residue is dissolved in 10 ml. of anhydrous ethanol, and the solution is left to crystallize at 0° to 2° C for 10 hours. 0.66 g. of apovincaminic acid ethyl ester are obtained (yield: 66%). On the basis of layer chromatography, a uniform product is formed. M.p.: 144° C (Boetius).

Workup

  1. temperatureunder reflux for 3 hours
  2. temperatureThe solution is cooled
  3. customevaporated to dryness under reduced pressure
  4. dissolutionThe dry residue is dissolved in 500 ml
  5. filtrationof 2% aqueous sulfuric acid, and the solution is filtered
  6. extractionThe mixture is extracted with 200 ml
  7. customportions of methylene chloride until no positive Mayer reaction
  8. customThe organic phases are separated
  9. dry with materialdried over anhydrous potassium carbonate
  10. filtrationfiltered
  11. customevaporated to dryness under reduced pressure
  12. dissolutionThe dry residue is dissolved in 10 ml
  13. waitof anhydrous ethanol, and the solution is left
  14. customto crystallize at 0° to 2° C for 10 hours

Sources & evidence

ORD record
ord-311fcc7f5b0a4a26b9fb8000e103174e
Source dataset
uspto-grants-1977_07
Patent number
US04035370

Linked notes

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