3-Bromo-4-methyl-5-(trifluoromethyl)pyridine synthesis

Yield:1211518-50-1 17.92%

Reaction Conditions:

Stage #1: 3-bromo-5-(trifluoromethyl)pyridinewith n-butyllithium;diisopropylamine in tetrahydrofuran at -100 - -10;
Stage #2: methyl iodide in tetrahydrofuran at -78; for 0.5 h;

Steps:

153

Example 153Preparation of 1-(benzo[d]thiazol-6-yl)-3-(4-methyl-5-(trifluoromethyl)pyridin-3-yl)imidazolidin-2-one, Trifluoroacetic Acid Salt (153A) Preparation of Starting Material 3-Bromo-4-methyl-5-trifluoromethyl-pyridine (SM-153a)Butyl Lithium (1.9 mL, 3.044 mmol) was added to a solution of DIPA (335.7 mg, 3.318 mmol) in THF (6 mL) at -78° C. The reaction mixture was stirred at -10° C. for 10 minutes. This was followed by the addition of 3-bromo-5-trifluoromethyl-pyridine (500 mg, 2.212 mmol) in THF (3 mL) at -100° C. The reaction mixture was stirred for a further 15 minutes at -90° C. and was followed by the addition of methyl iodide (557.0 mg, 3.924 mmol) in THF (2 mL) at -78° C. with stirring over a period of 30 minutes. The reaction was monitored by TLC (5% ethylacetate in hexane). The reaction mixture was quenched with aqueous NaHCO₃ solution and extracted with ethylacetate (100 mL). The organic layer was dried over Na₂SO₄ and concentrated. Purification by column chromatography on silica gel (2% ethylacetate in hexane) afforded 95 mg of the product (17.92% yield).LCMS: m/z=239.8 (M+1)

References:

US2010/331326,2010,A1 Location in patent:Page/Page column 60