Water → HCID 23468881, compound

HRID 128304Notes

Reaction equation

HRID 128304 reaction equation
C[N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][C:14]([CH3:16])=[CH:13][C:12]=3[CH:17]=2)[CH2:4][CH2:3]1.ClC(OCC)=O.[OH-].[K+].O>C1(C)C=CC=CC=1.C(O)COCCO>[CH3:16][C:14]1[O:15][C:11]2[CH:10]=[CH:9][C:8]([CH:5]3[CH2:6][CH2:7][NH:2][CH2:3][CH2:4]3)=[CH:17][C:12]=2[CH:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10928Ethyl chloroformateHCID 14797Potassium HydroxideHCID 23468846HCID 23468846, compound

Product 1

HCID 23468881HCID 23468881, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8117Diethylene GlycolSolvent

Procedure

7.3 g (0.03 mol) of 1-methyl-4-(2-methyl-5-benzofuranyl)-piperidine (c.f. Example 11) are stirred, together with 11.0 g (0.1 mol) of ethyl chloroformate, in 125 ml of toluene at 50°-55° for 15 hours. The solvent and excess ethyl chloroformate are distilled off under a waterpump vacuum at a bath temperature of 70°, the resulting residue is dissolved in toluene and the toluene solution is washed with water, 2 N sodium hydroxide solution, water, 2 N hydrochloric acid and water again. The toluene solution is then dried over sodium sulfate and evaporated to dryness under a waterpump vacuum. Crude ethyl 4-(2-methyl-2-benzofuranyl)-1-piperidinecarboxylate which remains as an oil can be further used directly. 9.1 g (0.03 mol) of the above crude ester and 15 g of solid potassium hydroxide are dissolved in 55 ml of diethylene glycol and 10 ml of water and the solution is refluxed for 15 hours in a nitrogen atmosphere. After cooling, the reaction mixture is diluted with 250 ml of toluene and the organic phase is separated off, washed with water and then extracted with 10% aqueous methanesulfonic acid solution. The acid extract is washed with toluene, rendered strongly alkaline in the cold with concentrated sodium hydroxide solution and extracted with chloroform. The chloroform solution is washed with water, dried over sodium sulfate and evaporated under a waterpump vacuum. The resulting oil is distilled under a high vacuum and gives 4-(2-methyl-5-benzofuranyl)-piperidine of boiling point 108°-111°/0.015 mm Hg.

Workup

  1. distillationThe solvent and excess ethyl chloroformate are distilled off under a waterpump vacuum at a bath temperature of 70°
  2. dissolutionthe resulting residue is dissolved in toluene
  3. washthe toluene solution is washed with water, 2 N sodium hydroxide solution, water, 2 N hydrochloric acid and water again
  4. dry with materialThe toluene solution is then dried over sodium sulfate
  5. customevaporated to dryness under a waterpump vacuum
  6. temperatureAfter cooling
  7. customthe organic phase is separated off
  8. washwashed with water
  9. extractionextracted with 10% aqueous methanesulfonic acid solution
  10. extractionThe acid extract
  11. washis washed with toluene
  12. extractionextracted with chloroform
  13. washThe chloroform solution is washed with water
  14. dry with materialdried over sodium sulfate
  15. customevaporated under a waterpump vacuum
  16. distillationThe resulting oil is distilled under a high vacuum

Sources & evidence

ORD record
ord-0d02c07ad1654b4bbfcb08adb34e54ff
Source dataset
uspto-grants-1981_03
Patent number
US04259338

Reaction notes

Loading…