Isopropanol → 6-Methylthio-5-trifluoromethyl-nicotinic acid
Reaction equation
[CH3:1][S:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6](Br)=[CH:5][N:4]=1.[C]=[O:15].[CH:16]([OH:19])(C)C>C(N(CC)CC)C.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>[CH3:1][S:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][C:6]([C:16]([OH:19])=[O:15])=[CH:5][N:4]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 130 °C
Procedure
The product of Example 7 (2.0 g, 7.4 mmol) was dissolved in a mixture of isopropanol (8 mL) and triethylamine (4 mL) in a 45 mL Hastelloy bomb. Bis(triphenylphosphine)palladium (II) chloride (0.1 g) was added and the vessel charged with carbon monoxide to a pressure of 300 psi. The reaction mixture was heated to 130° C. for 17 hours, allowed to cool to room temperature, and the pressure released. The reaction mixture was diluted with ethyl acetate (25 mL), filtered, and the solvents evaporated under reduced pressure. The residual oil was dissolved in ethyl acetate (50 mL) and washed with water and brine. Evaporation of the solvent under reduced pressure and purification of the resultant oil by chromatography over silica (5% ethyl acetate:hexane) gave 6-methylthio-5-trifluoromethyl-nicotinic acid: isopropyl ester as a clear oil (1.8 g).
Workup
- temperatureto cool to room temperature
- filtrationfiltered
- customthe solvents evaporated under reduced pressure
- dissolutionThe residual oil was dissolved in ethyl acetate (50 mL)
- washwashed with water and brine
- customEvaporation of the solvent
- customunder reduced pressure and purification of the resultant oil by chromatography over silica (5% ethyl acetate:hexane)
Sources & evidence
- ORD record
- ord-d55e16184ce3485e894f39dcb2b86350
- Source dataset
- uspto-grants-1999_10
- Patent number
- US05968875
Reaction notes
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