METHYL 2,6-DIFLUOROBENZOATE

General procedure: A catalytic amount of concentrated H2SO4 wasadded to a solution of carboxylic acids 16(a–j) (1.0 mmol)in 50 mL of methanol, and the mixture was refluxed for 6 h. It was allowed to cool. The saturated solution ofNaHCO3 was added to the reaction mixture, and it wasextracted with EtOAc (2 X 50 mL). The combined organiclayer was dried Na2SO4 and concentrated to obtain puremethyl esters 17(a–j).To a suspension of 2, 6-difluorobenzoic acid (50 g, 316 mmol) in MeOH (800 mL) was added TsOH ( 6 g, 10percent), the mixture was heated to reflux overnight. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc and washed with saturated NaHCO3 and brinesuccessively. The organic layer was separated, dried over NaStep 2: methyl 2, 6-difluorobenzoateTo a solution of 2, 6-difluorobenzoic acid (100 g, 0.63 mol) in sulfurous dichloride (150 mL) and the resulting reaction mixture was heated to refluxing for 2 hrs. Sulfurous dichloride was removed in vacuo, the residue in pyridine (100 ml) was added MeOH (100 mL) slowly and stirred at room temperature for 2 hrs. The solvent was removed in vacuo, the residue was dissolved in EtOAc (200 mL) and washed with aqueous NaOH (IN), HC1 (IN) and brine. The solution was dried over Na2, 6-difluorobenzoic acid (10 (^, 0.63111001) was dissolved in thionyl chloride (1501 ^), and the resulting mixture was heated under reflux for 2 hours. The excess sodium sulfoxide was distilled off and the resulting residue (100 mL) was added dropwise and the methanol was slowly added dropwise (100 mL). The reaction was stirred at room temperature for 2 hours and the solvent was removed in vacuo to remove the solvent. The resulting oil was dissolved in 200 mL of ethyl acetate and treated with IN sodium hydroxide solution, IN hydrochloric acid , Water and saturated salt water. After evaporation of the solvent in vacuo, the title compound (78.8 g, 73percent) was obtained as an oil.To a solution of 2, 6-difluorobenzoic acid (30.0 g, 190.0 mmol) in MeOH (100 mL) was added concentrated sulfuric acid (5 mL) dropwise at room temperature. The reaction mixture was heated under reflux overnight. The solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with saturated NaHCOGeneral procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 °C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I

Molecular Weight:172.13
XLogP3:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:172.03358575
Monoisotopic Mass:172.03358575
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes