Nitric Acid → HCID 59441933, compound

Participants

Reaction Steps

To a solution of 5-fluoro-1H-indole (5.0 g, 37 mmols) in acetic acid (300 ml) was added sodium cyanoborohydride (2.79 g, 44 mmols). After stirring overnight at rt, the reaction was concentrated under reduced pressure, redissolved in ethyl acetate (300 ml) and the pH was adjusted to 8 with saturated sodium bicarbonate. The organic layer was separated, filtered through a cotton plug, evaporated, and placed on the high vacuum for one hour prior to the next synthetic step. The crude material was then dissolved in acetic acid (100 ml), followed by the addition of acetic anhydride (3.5 ml, 37 mmols). After heating at 60 C for one hour, the reaction was poured into ice, stirred for one hour, solid was removed by vacuum filtration, rinsed with water and allowed to dry overnight under house vacuum. Next, to a solution of the 1-acetyl-5-fluoro-2,3-dihydro-1H-indole (500 mg, 2.79 mmol) in sulfuric acid (10 ml) at OC was added nitric acid (0.196 ml, 3.07 mmols) by a slow dropwise addition. After stirring 30 min at OC, the reaction was quenched by pouring into ice water. The solids were removed by vacuum filtration, redissolved in dichloromethane (50 ml), adsorbed to silica gel, and purified by LC(25% to 75% ethyl acetate/hexanes). The lower Rf spot was isolated and the structure was determined to be the desired regioisomer by IR profiling. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.18 (s, 3 H) 3.25 (t, J=8.63 Hz, 2 H) 4.18 (t, J=8.53 Hz, 2 H) 7.50 (d, J=11.24 Hz, 1 H) 8.64 (d, J=7.22 Hz, 1 H).

Provenance & Evidence