Ammonia → HCID 20137909, compound

HRID 1253001Notes

Reaction equation

HRID 1253001 reaction equation
[C:1]([O:4][C:5]1([CH2:12][NH2:13])[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1)(=[O:3])C.[CH:14](N)=[O:15].N.C[OH:19]>O1CCCC1>[C:14]([OH:15])(=[O:19])[C:1]([OH:4])=[O:3].[CH3:11][N:8]1[CH2:7][CH2:6][C:5]([CH2:12][NH:13][CH3:14])([OH:4])[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 713FormamideHCID 887MethanolHCID 14153812HCID 14153812, compound

Product 1

HCID 20137909HCID 20137909, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 46 g (0.23 mole) of 4-(aminomethyl)-1-methyl-4-piperidinol acetate [1:1] and 10.2 g (0.23 mole) of formamide was stirred at 160° C. until evolution of ammonia ceased (about 24 hr). The reaction mixture was dissolved in 150 ml of tetrahydrofuran and treated dropwise at reflux with 101 ml (1.01 mole) of 10M borane-methylsufide. Reflux was continued for 5.5 hr and the mixture was allowed to stand at room temperature over the weekend. Approximately 200 ml of methanol was added dropwise and the mixture was heated to reflux for 1 hr. Hydrogen chloride gas was bubbled into the mixture until a pH of <1 persisted. The mixture was heated to reflux for 3 hr and filtered. The filtrate was treated with 500 ml of dilute sodium hydroxide and extracted 4 times with ether. The aqueous layer was continuously extracted with chloroform for 24 hr. The chloroform was concentrated to give 22 g of residue. A 20 g sample was dissolved in 80 ml of ethanol. The resulting crystals were recrystallized from methanol-water to give 15 g of crystals, m.p. 197°-199° C.

Workup

  1. custom(about 24 hr)
  2. additiontreated dropwise
  3. temperatureReflux
  4. customto stand at room temperature over the weekend
  5. temperaturethe mixture was heated
  6. temperatureto reflux for 1 hr
  7. customHydrogen chloride gas was bubbled into the mixture until a pH of <1
  8. temperatureThe mixture was heated
  9. temperatureto reflux for 3 hr
  10. filtrationfiltered
  11. additionThe filtrate was treated with 500 ml of dilute sodium hydroxide
  12. extractionextracted 4 times with ether
  13. extractionThe aqueous layer was continuously extracted with chloroform for 24 hr
  14. concentrationThe chloroform was concentrated

Sources & evidence

ORD record
ord-dd0935a9b8a844c5808fddd9100f56e3
Source dataset
uspto-grants-1988_05
Patent number
US04746655

Reaction notes

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