2-Bromo-3-methylthiophene → HCID 46316027, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-bromo-3-methylthiophene (5 g, 28.24 mmol), pyridin-4-ylboronic acid (4.2 g, 33.89 mmol), and saturated sodium bicarbonate (70.60 mL of 1.2 M, 84.72 mmol) in DMF (100 mL) was degassed with nitrogen. PdCl2(dppf) (1.239 g, 1.694 mmol) was added and the reaction mixture heated at 90° C. under an atmosphere of nitrogen for 14 hours. After cooling, the mixture was poured into a saturated NaHCO3 solution, which was extracted with EtOAc. The organics were washed with saturated NaHCO3, dried over MgSO4, and the volatiles were removed by evaporation. The residue was purified by medium pressure silica gel chromatography, eluting with 1%-50% EtOAc/hexanes, to afford 4-(3-methylthiophen-2-yl)pyridine (3 g, 61% yield) as slightly yellow oil; 1H NMR (300 MHz, CDCl3): δ 8.54 (dd, J=1.6, 4.5 Hz, 2H), 7.30 (dd, J=1.7, 4.5 Hz, 2H), 7.23 (d, J=5.1 Hz, 1H), 6.88 (d, J=5.1 Hz, 1H) and 2.32 (s, 3H). This compound (3 g, 17.12 mmol) was dissolved in acetonitrile (100 mL) and NBS (3.047 g, 17.12 mmol) was added at RT. The reaction mixture was stirred at RT for 24 hours and the reaction quenched by adding an aqueous solution of Na2SO3 and saturated NaHCO3 solution. The resulting precipitate was collected and washed with water. After drying under high vacuum, 4-(5-bromo-3-methylthiophen-2-yl)pyridine (Compound 1067, 4 g, 92%) was obtained as yellow solid; ESMS (M+H)=254.05; 1H NMR (300 MHz, DMSO-d6): δ 8.74 (dd, J=1.5, 5.0 Hz, 2H), 7.78 (dd, J=1.5, 5.0 Hz, 2H), 7.46 (s, 1H) and 2.46 (s, 3H).

Provenance & Evidence