Potassium Hydroxide → Brofaromine

HRID 486290Notes

Reaction equation

HRID 486290 reaction equation
[Br:1][C:2]1[C:10]2[O:9][C:8]([CH:11]3[CH2:16][CH2:15][N:14](C(OCC)=O)[CH2:13][CH2:12]3)=[CH:7][C:6]=2[CH:5]=[C:4]([O:22][CH3:23])[CH:3]=1.[OH-].[K+]>C(O)CO.C1(C)C=CC=CC=1>[Br:1][C:2]1[C:10]2[O:9][C:8]([CH:11]3[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]3)=[CH:7][C:6]=2[CH:5]=[C:4]([O:22][CH3:23])[CH:3]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 111434314-(7-Bromo-5-methoxy-benzofuran-2-yl)-1-ethoxycarbonyl-piperidine

Product 1

HCID 44571Brofaromine

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 1140TolueneSolvent

Procedure

7.6 g of 4-(7-bromo-5-methoxy-benzofuran-2-yl)-1-ethoxycarbonyl-piperidine are dissolved in 80 ml of ethylene glycol. After the addition of 19.4 g of 86% potassium hydroxide, the resulting cloudy solution is heated at 160° with vigorous stirring for 18 hours. The reaction mixture is cooled to 100°, diluted with 80 ml of toluene, and cooled further to 20°. The reaction solution is extracted twice with 1000 ml of water each time and then four times with 200 ml of a 10% solution of methanesulfonic acid in water each time. The resulting solution in methanesulfonic acid is adjusted to pH 12 by the addition of 30% sodium hydroxide solution and extracted by shaking with 1000 ml of chloroform. The chloroform solution is dried over sodium sulfate, filtered and concentrated by evaporation. Crystallisation from ethyl acetate yields 4-(7-bromo-5-methoxybenzofuran-2-yl)-piperidine having a melting point of 149°-152°. There is obtained from the base by treatment with methanolic hydrochloric acid and recrystallisation from methanol/ether 4-(7-bromo-5-methoxy-benzofuran-2-yl)-piperidine-hydrochloride having a melting point of 242°-243°.

Workup

  1. temperaturethe resulting cloudy solution is heated at 160°
  2. temperatureThe reaction mixture is cooled to 100°
  3. temperaturecooled further to 20°
  4. extractionThe reaction solution is extracted twice with 1000 ml of water each time
  5. additionThe resulting solution in methanesulfonic acid is adjusted to pH 12 by the addition of 30% sodium hydroxide solution
  6. extractionextracted
  7. stirringby shaking with 1000 ml of chloroform
  8. dry with materialThe chloroform solution is dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated by evaporation
  11. customCrystallisation from ethyl acetate

Sources & evidence

ORD record
ord-2926f403d301454f99ad9142dc4b6a0f
Source dataset
uspto-grants-1994_03
Patent number
US05290939

Reaction notes

Loading…