Methanamine, hydrochloride (1:1) → 1-[4-(Methylamino)piperidin-1-yl]ethan-1-one--hydrogen chloride (1/1)

HRID 1577839Notes

Reaction equation

HRID 1577839 reaction equation
[OH-].[K+].[Cl-:3].C[NH3+].[C:6]([N:9]1[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]1)(=[O:8])[CH3:7].[C:16]([BH3-])#[N:17].[Na+]>CO.C(O)C.C(O)(C)C>[ClH:3].[C:6]([N:9]1[CH2:14][CH2:13][CH:12]([NH:17][CH3:16])[CH2:11][CH2:10]1)(=[O:8])[CH3:7]

Participants

8

Reactant 4

HCID 11637Methanamine, hydrochloride (1:1)HCID 14797Potassium Hydroxide2×HCID 122563N-Acetyl-4-piperidoneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 205698961-[4-(Methylamino)piperidin-1-yl]ethan-1-one--hydrogen chloride (1/1)Yield 71.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolvent2×HCID 3776IsopropanolSolvent

Procedure

Potassium hydroxide flakes (2 g) were added to a solution of methylammonium chloride (8.5 g) in methanol (75 ml) at 0°-5°. 1-Acetylpiperid-4-one (14 g) was then added, the mixture stirred for 15 minutes and then a solution of sodium cyanoborohydride (2.5 g) in methanol (25 ml) was added over a period of 30 minutes. The mixture was stirred at room temperature overnight and then potassium hydroxide (6 g) was added. After filtration through sodium carbonate, the filtrate was evaporated to dryness and the residue was partitioned between chloroform (100 ml) and aqueous potassium hydroxide (2.5 g in 15 ml H2O). The chloroform layer was dried (Na2CO3) and evaporated to give a colorless oil which was dissolved in a mixture of ethanol (40 ml) and isopropyl alcohol (40 ml), then excess hydrogen chloride gas was bubbled into the cooled solution (ice bath). Addition of acetone resulted in the slow crystallization of 1-acetyl-4-methylaminopiperidine hydrochloride (5.5 g) (identified by n.m.r.).

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. filtrationAfter filtration through sodium carbonate
  3. customthe filtrate was evaporated to dryness
  4. customthe residue was partitioned between chloroform (100 ml) and aqueous potassium hydroxide (2.5 g in 15 ml H2O)
  5. dry with materialThe chloroform layer was dried (Na2CO3)
  6. customevaporated
  7. customto give a colorless oil which
  8. customexcess hydrogen chloride gas was bubbled into the cooled solution (ice bath)
  9. additionAddition of acetone

Sources & evidence

ORD record
ord-03fb3f0c01e7486fbd0eaea76ba78402
Source dataset
uspto-grants-1981_09
Patent number
US04289772

Reaction notes

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