Methylamine → Ethyl 4-hydroxy-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylate

HRID 15929

Reaction equation

HRID 15929 reaction equation
C(O[C:4](=[O:15])[CH:5]([CH3:14])[C:6](=[O:13])[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])C.C(OC(O[CH2:22][CH3:23])=C)C.[CH3:24][NH2:25]>C(OCC)C.C[O-].[Na+]>[CH2:11]([O:10][C:8]([C:7]1[C:6]([OH:13])=[C:5]([CH3:14])[C:4](=[O:15])[N:25]([CH3:24])[C:22]=1[CH3:23])=[O:9])[CH3:12]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 1376731,1-DiethoxyetheneHCID 10921903Diethyl 2-methyl-3-oxopentanedioate

Product 1

HCID 66673467Ethyl 4-hydroxy-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylateYield 34%

Reagents, catalysts & solvents 2

HCID 10942334Sodium MethoxideCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-methyl-3-oxo-pentanedioic acid diethyl ester (10.0 g, 46.3 mmol), 1,1-diethoxy-ethene (12.8 mL, 92.5 mmol) and sodium methoxide (0.026 mg, 0.481 mmol) was heated to 85° C. for nine hours. The reaction mixture was cooled to room temperature and concentrated. To the resulting residue was added methylamine (1.91 mL, 55.5 mmol, 40% H2O). After stirring at room temperature for 16 hours, the reaction mixture was diluted with diethyl ether and washed with water. The aqueous phase was acidified to pH 1 with 10% HCl solution and extracted with EtOAc. The organic layer was dried (MgSO4) and concentrated. Trituration of the resulting residue with diethyl ether and flash column chromatography (3% MeOH in methylene chloride) gave 3.55 g (34%) desired product.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. washwashed with water
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-4177aaa645f44dd69db93fa00123b3e9
Source dataset
uspto-grants-2010_06
Patent number
US07732616B2

Linked notes

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