Methylamine → 3,5-Dimethyl 1-methyl-4-oxo-2,6-di-2-pyridinyl-3,5-piperidinedicarboxylate

HRID 1685997Notes

Reaction equation

HRID 1685997 reaction equation
[CH3:1][O:2][C:3]([CH2:5][C:6]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[O:7])=[O:4].[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH:19]=O.[CH3:21][NH2:22]>C(O)C(C)C>[CH3:21][N:22]1[CH:19]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=2)[CH:8]([C:9]([O:11][CH3:12])=[O:10])[C:6](=[O:7])[CH:5]([C:3]([O:2][CH3:1])=[O:4])[CH:19]1[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=1

Participants

5

Reactant 3

HCID 6329MethylamineHCID 142732-PyridinecarboxaldehydeHCID 74591Dimethyl 3-oxoglutarate

Product 1

HCID 120155943,5-Dimethyl 1-methyl-4-oxo-2,6-di-2-pyridinyl-3,5-piperidinedicarboxylateYield 880.3%

Reagents, catalysts & solvents 1

HCID 6560IsobutanolSolvent

Conditions

Temperature
10 °C

Procedure

1st stage: 12.9 kg of dimethyl acetonedicarboxylate (97%; 72 mol) were dissolved in 52.5 l of isobutanol. The solution was cooled to 10° C. At this temperature, 15.4 kg of pyridine-2-aldehyde (14.4 mol) were added dropwise and the mixture was stirred for a further 10 minutes. Subsequently, 5.59 kg of methylamine (40% in water, 72 mol) were added dropwise to this mixture at such a rate that the temperature could be maintained with uniform cooling. The reaction mixture was stirred at 10° C. for a further 90 minutes. After the reaction time had ended, the mixture was heated to 40-45° C. and 6.6 kg of water phase were separated out under reduced pressure at internal temperature 40-45° C. with the aid of a water separator. The mixture was then vented and cooled to 5-10° C. The product was filtered off and washed with 7.5 l of isobutanol. The moist product was dried at 50° C. under reduced pressure. 24.3 kg (88%) of 1-methyl-2,6-dipyridyl-3,5-di(methoxy-carbonyl)-4-piperidone were obtained as a white-beige powder.

Workup

  1. temperaturecould be maintained with uniform cooling
  2. stirringThe reaction mixture was stirred at 10° C. for a further 90 minutes
  3. temperaturethe mixture was heated to 40-45° C.
  4. custom6.6 kg of water phase were separated out under reduced pressure at internal temperature 40-45° C. with the aid of a water separator
  5. temperaturecooled to 5-10° C
  6. filtrationThe product was filtered off
  7. washwashed with 7.5 l of isobutanol
  8. customThe moist product was dried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-a1eccb170acb4d2189483c69e82fe23a
Source dataset
uspto-grants-2012_04
Patent number
US08148530B2

Reaction notes

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