Formic Acid → HCID 22712051, compound

HRID 1167579Notes

Reaction equation

HRID 1167579 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

From 47.4 g of 1-benzyl-4-(3-hydroxypropylamino)-piperidine-dihydrochloride the base is liberated, 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 it is stirred for another hour at about 100-110° C. It is left to cool, combined with 150 ml of methanol, made alkaline with about 270 ml of 32% sodium hydroxide solution with cooling and stirred for about another 30 minutes at 40-50° C. and then the methanol is distilled off. The residue is extracted with twice 100 ml of methylene chloride, the combined methylene chloride phases are dried, filtered and freed from solvent in vacuo. The residue is taken up in 80 ml Ethanol, acidified with 34 ml of 32% hydrochloric acid, combined with 100 ml of acetone and stirred. As soon as crystals have been precipitated more 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 in the form of a solid.

Workup

  1. waitThe mixture is left
  2. temperatureto cool
  3. stirringit is stirred for another hour at about 100-110° C
  4. waitIt is left
  5. temperatureto cool
  6. temperaturewith cooling
  7. stirringstirred for about another 30 minutes at 40-50° C.
  8. distillationthe methanol is 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 have been precipitated more acetone
  14. additionis added
  15. filtrationfiltered
  16. washwashed with acetone
  17. customdried

Sources & evidence

ORD record
ord-68b0fce035714109bc21aa9ca6a7ee69
Source dataset
uspto-grants-2003_09
Patent number
US06620438B2

Reaction notes

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