Piperidine → Methyl 3-(4-methoxypyridin-2-yl)acrylate

HRID 1179425Notes

Reaction equation

HRID 1179425 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]=O)[CH:4]=1.Cl.N1C=CC=CC=1.[K+].[C:19]([O:25][CH3:26])(=[O:24])[CH2:20]C([O-])=O.N1CCCCC1>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH:9]=[CH:20][C:19]([O:25][CH3:26])=[O:24])[CH:4]=1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 2724687Potassium methyl malonateHCID 10176127Pyridinium chlorideHCID 123253904-Methoxypyridine-2-carbaldehyde

Product 1

HCID 68407789Methyl 3-(4-methoxypyridin-2-yl)acrylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 45 g of 4-methoxypyridine-2-carbaldehyde (Ashimori et al., Chem.Pharm.Bull. 38, 2446-2458 (1990)), 75.80 g of pyridine hydrochloride, 102.45 g of monomethyl malonate potassium salt and 4.1 ml of piperidine in 700 ml of pyridine are slowly heated, with stirring, to 120° C. When the evolution of gas starts, the heating source is temporarily removed to stop the reaction from becoming too violent. Once the reaction has subsided, the mixture is stirred at 120° C. for a further 2.5 hours, and the pyridine is then distilled off under reduced pressure. The residue is partitioned between ethyl acetate/water and the organic phase is washed with water and dried. The residue obtained after concentration is chromatographed on a silica gel column using ethyl acetate/petroleum ether 2:1. This initially gives 43.2 g of the title compound as a yellow oil which crystallizes on standing and then shows a m.p. of 80-82° C. The mass spectrum shows the molecular peak MH+ at 194 Da.

Workup

  1. temperatureare slowly heated
  2. customWhen the evolution of gas starts, the heating source is temporarily removed
  3. customthe reaction
  4. stirringthe mixture is stirred at 120° C. for a further 2.5 hours
  5. distillationthe pyridine is then distilled off under reduced pressure
  6. customThe residue is partitioned between ethyl acetate/water
  7. washthe organic phase is washed with water
  8. customdried
  9. customThe residue obtained
  10. concentrationafter concentration
  11. customis chromatographed on a silica gel column
  12. customThis initially gives 43.2 g of the title compound as a yellow oil which crystallizes

Sources & evidence

ORD record
ord-6074bb58e90b452185a2ae66e8db5cae
Source dataset
uspto-grants-2007_10
Patent number
US07279488B2

Reaction notes

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