Cesium fluoride → Methyl 4-amino-3-chloro-5-fluoro-6-vinylpyridine-2-carboxylate

HRID 2113413Notes

Reaction equation

HRID 2113413 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14].[CH2:15]([Sn](CCCC)(CCCC)C=C)[CH2:16]CC.[F-].[Cs+]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([CH:15]=[CH2:16])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14]

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 81998TributylvinyltinHCID 22677265Methyl 4-amino-3,6-dichloro-5-fluoropicolinate

Product 1

HCID 67026737Methyl 4-amino-3-chloro-5-fluoro-6-vinylpyridine-2-carboxylateYield 67.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of methyl 4-amino-3,6-dichloro-5-fluoropyridine-2-carboxylate (8.00 g, 33.0 mmol), tributyl(vinyl)tin (13.27 g, 42.0 mmol) and cesium fluoride (11.19 g, 73.6 mmol) in dimethylformamide (250 mL) was sparged with nitrogen for 15 minutes. Dichlorobis(triphenylphosphine)palladium (II) (1.17 g, 1.6 mmol) was then added and the mixture was heated at 90° C. overnight. After cooling, the mixture was concentrated, taken up into ethyl acetate and filtered through a silica gel plug. The solvents were removed and the crude product was purified by column chromatography (50% ethyl acetate in hexane) to give methyl 4-amino-3-chloro-5-fluoro-6-vinylpyridine-2-carboxylate (5.13 g, 22.2 mmol), mp 68-71° C.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated
  3. filtrationfiltered through a silica gel plug
  4. customThe solvents were removed
  5. customthe crude product was purified by column chromatography (50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8ecb7cec0a2d499982da6031aa5121ae
Source dataset
uspto-grants-2008_10
Patent number
US07432227B2

Reaction notes

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