Formic Acid → HCID 22712051, compound

HRID 352429Notes

Reaction equation

HRID 352429 reaction equation
[ClH:1].Cl.[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([NH:16][CH2:17][CH2:18][CH2:19][OH:20])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:21](O)=O.C=O.[OH-].[Na+]>CO>[ClH:1].[ClH:1].[CH2:3]([N:10]1[CH2:11][CH2:12][CH:13]([N:16]([CH2:17][CH2:18][CH2:19][OH:20])[CH3:21])[CH2:14][CH2:15]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 284Formic Acid2×HCID 712Formaldehyde2×HCID 14798Sodium HydroxideHCID 22712046HCID 22712046, compound

Product 1

HCID 22712051HCID 22712051, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
95 °C

Procedure

The base is liberated from 47.4 g of 1-benzyl-4-(3-hydroxypropylamino)-piperidine-dihydrochloride, combined with 63 ml of 85% formic acid and 22 ml of 37% formaldehyde solution and stirred for two hours at about 90-100° C. The mixture is left to cool, 37 ml of formic acid and 11 ml of formaldehyde solution are added and stirred for another hour at about 100-110° C. The mixture is left to cool, combined with 150 ml of methanol, made alkaline with about 270 ml of 32% sodium hydroxide solution while cooling and stirred for about another 30 minutes at 40-50° C. and the methanol is then distilled off. The residue is extracted with twice 100 ml of methylene chloride, the combined methylene chloride phases are dried, filtered and the solvent is eliminated in vacuo. The residue is taken up in 80 ml of ethanol, acidified with 34 ml of 32% hydrochloric acid, combined with 100 ml of acetone and stirred. As soon as crystals are precipitated, further acetone is added. The precipitate is suction filtered, washed with acetone and dried. 42.8 g of 1-benzyl-4-[-(3-hydroxypropyl)-methylamino]-piperidine-dihydrochloride are obtained as a solid.

Workup

  1. waitThe mixture is left
  2. temperatureto cool
  3. stirringstirred for another hour at about 100-110° C
  4. waitThe mixture is left
  5. temperatureto cool
  6. temperaturewhile cooling
  7. stirringstirred for about another 30 minutes at 40-50° C.
  8. distillationthe methanol is then distilled off
  9. extractionThe residue is extracted with twice 100 ml of methylene chloride
  10. dry with materialthe combined methylene chloride phases are dried
  11. filtrationfiltered
  12. stirringstirred
  13. customAs soon as crystals are precipitated
  14. additionfurther acetone is added
  15. filtrationfiltered
  16. washwashed with acetone
  17. customdried

Sources & evidence

ORD record
ord-ee597c2d87c64c9aab150eeaf21d6e87
Source dataset
uspto-grants-2004_06
Patent number
US06747044B2

Reaction notes

Loading…