Bromine → 1-(5-Bromo-3-fluoropyridin-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxylic acid

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Reaction Steps

A 500 mL round bottom flask fitted with a rubber septum was charged with 10 grams of 1-(3-fluoropyridin-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxylic acid 21 (45 mMol) and dissolved in 170 mL dichloromethane (DCM). With a syringe, 1.1 equivalents bromine (49.5 mMol) was added slowly to the solution. The reaction was allowed to progress at room temperature for 18 hours. The precipitate was collected by vacuum filtration and washed with 2×100 mL DCM. The filter cake was transferred to a 2 L beaker and covered with 300 mL 1N aq. sodium hydroxide, and stirred with a magnetic stir bar until all solids dissolved. The solution was transferred to a 1000 mL extraction funnel and shaken with 2×100 mL ethyl acetate (EtOAc). The organic layer was discarded and the aqueous layer was acidified with 50 mL 2N aq.HCl. The crude compound 23 was extracted with 2×100 mL EtOAc. The organic layer was dried over sodium sulfate, concentrated under vacuum, and crystallized as white needles from hot EtOAc. 23: (55% white solid): m/z 301, 1H NMR (DMSO) δ 12.42 (s, 1H), 8.14-8.11 (m, 1H), 7.93-7.87 (m, 1H), 6.94-6.89 (m, 1H), 4.13-4.07 (m, 2H), 3.58-3.52 (m, 2H), 2.40-2.33 (m, 2H).

Provenance & Evidence