477252-20-3

75-16-1

62150-47-4

477252-20-3

1. Assemble a 3 L three-necked round-bottomed flask equipped with a dropping funnel, reflux condenser, nitrogen inlet, and temperature probe. 2. Add methylmagnesium bromide (3.2 M, dissolved in 2-methyltetrahydrofuran, 239.07 mL, 765.01 mmol) to the flask and cool to 0°C in an ice bath. 3. A solution of ethyl 4-bromopyridine-2-carboxylate (80.0 g, 347.73 mmol) in tetrahydrofuran (THF, 800.0 mL) was added to a dropping funnel. 4. The THF solution of ethyl 4-bromopyridine-2-carboxylate was slowly added dropwise to a solution of methylmagnesium bromide, with the dropwise acceleration being controlled to keep the reaction temperature below 25°C. The reaction was completed with the addition of ethyl 4-bromopyridine-2-carboxylate (80.0 g, 347.73 mmol). 5. After the dropwise addition is complete, the ice bath is removed and the reaction mixture is stirred at 25°C for 30 minutes. 6. The reaction mixture was cooled to 5°C and a 1 M aqueous hydrochloric acid solution was slowly added dropwise, with controlled drop acceleration to maintain the internal temperature below 30°C, until the pH of the reaction mixture was neutral. 7. The organic layer was separated by diluting the reaction mixture with ethyl acetate (EtOAc, 200 mL). 8. The organic layer was dried with anhydrous sodium sulfate, filtered through a CELITE? plug and washed with EtOAc. 9. The filtrate was concentrated to give an orange colored oil. 10. Purification by silica gel column chromatography using hexane/EtOAc (3:1) as eluent gave 2-(4-bromopyridin-2-yl)-2-propanol (63.15 g, 84.0% yield) as a colorless oil. 11. Mass spectrometry (MS) analysis showed m/z: 216/218 ([M+1]/[M+3]).