Dimethylformamide → Methyl 2-vinylnicotinate

HRID 274854

Reaction equation

HRID 274854 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:12]([Sn](CCCC)(CCCC)CCCC)=[CH2:13].C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C.CN(C)C=O>[Pd].C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH:12]([C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1)=[CH2:13]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 314042,6-Di-tert-butyl-4-methylphenolHCID 81998Tributylvinyltin2×HCID 819931Methyl 2-chloronicotinate

Product 1

HCID 21862216Methyl 2-vinylnicotinate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

2-Ethenyl-3-pyridinecarboxylic acid, methyl ester (12) is prepared as follows: a mixture of 19.7 g (115 mmol) of 2-chloro-3-pyridinecarboxylic acid, methyl ester (11), 38.3 g (120.8 mmol) of vinyltributyltin, 1.48 g (2.1 mmol) of bis(triphenylphosphine)palladium (II) chloride 100 mg of 2,6-ditertbutyl-4-methylphenol, and 250 mL of N,N-dimethylformamide is stirred at 55° C. for 7 hours, then treated with 1.63 g 15.1 mmol) of additional vinyltributyltin and 1 g of palladium catalyst. The mixture is heated further at 40° C. for 61 hours, then concentrated at 60° C./5 mm to leave a greenish oil that is dissolved in ethyl acetate and filtered through a pad of silica gel (230-400 mesh). The filtrate is diluted with additional ethyl acetate and the organic phase is washed with water, dried, and concentrated to an oil. The oil is distilled, with material collected in the 80°-95° C./0.14 mm ranger to leave 24.5 g of an oil that is ca. 75% product by GC. The oil is dissolved in dichloromethane:hexanes (1:1) and loaded onto an 8 x 15 cm of silica gel column (230-400 mesh). The column is eluted with the same solvent as above with 500 mL fractions collected. Product fractions are combined and carefully distilled at 65°-67° C./0.15 mm to leave 13.6 g of clear oil, >95% pure by GC, that is sufficiently pure to use directly in the next step.

Workup

  1. temperatureThe mixture is heated further at 40° C. for 61 hours
  2. concentrationconcentrated at 60° C./5 mm
  3. customto leave a greenish oil that
  4. filtrationfiltered through a pad of silica gel (230-400 mesh)
  5. additionThe filtrate is diluted with additional ethyl acetate
  6. washthe organic phase is washed with water
  7. customdried
  8. concentrationconcentrated to an oil
  9. distillationThe oil is distilled, with material
  10. customcollected in the 80°-95° C./0.14 mm ranger

Sources & evidence

ORD record
ord-b7b5d8a724604f80800b2e11dc4c62c3
Source dataset
uspto-grants-1995_02
Patent number
US05391554

Linked notes

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