Potassium Hydroxide → Ethyl 3-methyl-4-(methylamino)-1-piperidinecarboxylate

HRID 746850Notes

Reaction equation

HRID 746850 reaction equation
Cl.CN.[C:4]([N:9]1[CH2:14][CH2:13][C:12](=O)[CH:11]([CH3:16])[CH2:10]1)([O:6][CH2:7][CH3:8])=[O:5].[OH-].[K+].[C:19]([BH3-])#[N:20].[Na+]>CO>[C:4]([N:9]1[CH2:14][CH2:13][CH:12]([NH:20][CH3:19])[CH:11]([CH3:16])[CH2:10]1)([O:6][CH2:7][CH3:8])=[O:5]

Participants

6

Reactant 4

HCID 14797Potassium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 6364545Methylamine hydrochlorideHCID 15075657Ethyl 3-methyl-4-oxopiperidine-1-carboxylate

Product 1

HCID 15725099Ethyl 3-methyl-4-(methylamino)-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Methylamine hydrochloride (10 g, 148 mmol) was added to the stirred solution of 1-carbethoxy-3-methyl-4-piperidone (7 g, 37.83 mmol) obtained as described in Preparation 1, in methanol (50 ml) followed by 8.3 g (148 mmol) KOH. Stirring was continued for 3 hr at ambient temperature. The resulting mixture was cooled at 0° C. and sodium cyanoborohydride (3.0 g, 46.0 mmol) was added to it. Cooling was removed after 10 min. and resulting mixture was stirred for 12 hr at ambient temperature. The reaction mixture was concentrated to dryness, triturated with water, acidified with conc. HCl (pH 3˜4) and extracted with ethyl acetate to remove impurities. The aqueous layer was basified with 1 M sodium hydroxide solution (pH ˜10) and extracted with ethyl acetate. Ethyl acetate extract was dried (Na2SO4) and concentrated to dryness to give 1-carbethoxy-4-methylamino-3-methylpiperidine. Yield 4.0 g (50%), C10H20N2O2, m/z 201 (M+1), PMR (CDCl3): 0.92 (dd, 3H), 1.26 (t, 3H), 1.54 (m, 1H), 2.1 (m, 2H), 2.34 (s, 3H), 2.62 (m, 1H), 2.86 (m, 1H), 3.06 (m, 1H), 3.46 (m, 1H), 3.72 (m, 1H), 4.1 (q, 2H).

Workup

  1. customobtained
  2. temperatureCooling
  3. customwas removed after 10 min.
  4. customresulting mixture
  5. stirringwas stirred for 12 hr at ambient temperature
  6. concentrationThe reaction mixture was concentrated to dryness
  7. customtriturated with water
  8. extractionextracted with ethyl acetate
  9. customto remove impurities
  10. extractionextracted with ethyl acetate
  11. extractionEthyl acetate extract
  12. dry with materialwas dried (Na2SO4)
  13. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-617909ba711646d2ad767c0e7d6b1edd
Source dataset
uspto-grants-2008_07
Patent number
US07393957B2

Reaction notes

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