Ethyl 3-Bromo-5-Fluoroisonicotinate synthesis

Yield:1214335-25-7 670 mg

Reaction Conditions:

Stage #1: 3-bromo-5-fluoropyridinewith lithium diisopropyl amide in tetrahydrofuran at -78; for 1 h;
Stage #2: chloroformic acid ethyl ester in tetrahydrofuran at -78 - 20; for 1 h;

Steps:

91 Synthesis of 3-(8-carbamoyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-5-fluoro-isonicotinic acid methyl ester (Cpd 211, Table 1)

To a round bottom flask is added 3-bromo-5-fluoropyridine (475 mg, 2.7 mmol) in 4 ml of dry THF at -78° C., followed by the addition of lithium diisopropylamine (1.62 ml, 3.24 mmol). The reaction mixture is stirred at -78° C. for 1 hour, followed by the addition of ethyl chloroformate (586 mg, 5.4 mmol). The reaction mixture is warmed up to room temperature and stirred for 1 hour. The reaction mixture is diluted with EtOAc, washed with saturated NH₄Cl/water, brine, dried over anhydrous Na₂SO₄, filtered and concentrated to give the crude product. Purification by the flash column chromatography affords 670 mg of 3-bromo-5-fluoro-isonicotinic acid ethyl ester.

References:

US2014/323468,2014,A1 Location in patent:Paragraph 0676