Toluene → 2-Chloro-6-(2-oxopropyl)-isonicotinic acid methyl ester

HRID 732398

Reaction equation

HRID 732398 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([Cl:12])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C[O-].C([Sn+](CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C([O:38][C:39]([CH3:41])=[CH2:40])(=O)C>C(OCC)C.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.Cl[Pd]Cl>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:3]=[C:2]([CH2:40][C:39](=[O:38])[CH3:41])[N:11]=[C:10]([Cl:12])[CH:9]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 7916Isopropenyl acetateHCID 93237Methyl 2,6-dichloroisonicotinateHCID 11964040Methoxytri-n-butylstannane

Product 1

HCID 860813562-Chloro-6-(2-oxopropyl)-isonicotinic acid methyl esterYield 29%

Reagents, catalysts & solvents 2

HCID 10876480Bis(tri-o-tolylphosphine)palladium(II) DichlorideCatalystHCID 3283Diethyl EtherSolvent

Procedure

Add methyl 2,6-dichloroisonicotinate (3.0 g, 15.0 mmol), trans-dichlorobis(tri-o-tolylphosphine)palladium (II) (196 mg, 0.25 mmol), tributyltin methoxide (2.4 g, 7.5 mmol) and toluene (20 mL) in a previously nitrogen filled sealed vessel. Flush the reactants with nitrogen again. Add isopropenyl acetate (0.85 mL, 7.75 mmol) under nitrogen and heat the sealed mixture at 100° C. overnight with vigorous stirring. Cool the reaction to room temperature, dilute with diethyl ether and filter through a filtering agent. Concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate:hexanes) to give the title compound (29%).

Workup

  1. additionfilled
  2. customsealed vessel
  3. customFlush the reactants with nitrogen again
  4. temperatureCool
  5. customthe reaction to room temperature
  6. filtrationfilter through a filtering agent
  7. concentrationConcentrate
  8. custompurify
  9. wash(silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-6cafdc01f40e4a8093bd56662c23170e
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Linked notes

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