Tetrahydrofuran → HCID 66735542, compound

Participants

Reaction Conditions

Reaction Steps

A 250 ml round bottom flask containing 5-fluoro-6-methylpyridine-2-carbonitrile (Method 15; 2.24 g, 16.45 mmol) was charged with anhydrous THF (20 ml) under N2. The solution was cooled to 0° C., and a solution of MeMgBr (8.5 ml of a 3.0 M solution in ether, 25.5 mmol) was added dropwise. After 1 hour at 0° C., the reaction was quenched with saturated NH4Cl (10 ml, added drop wise), and the biphasic mixture was allowed to stir at 0° C. for 10 minutes. The layers were then separated, and the aqueous portion was extracted with EtOAc, and the combined organics were washed with brine, dried, filtered, and concentrated. The resulting oil was dissolved in MeOH (20 ml), and the solution was cooled to 0° C. NaBH4 (634 mg, 16.8 mmol) was added in portions over 5 minutes. The reaction was allowed to stir at room temperature for 1 hour, and was then concentrated. The residue was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried, filtered, and concentrated. The crude material was purified by silica gel chromatography (Rf in 60:40 hexanes:EtOAc=0.42) to afford the title compound as a pale yellow oil (550 mg, 22% over two steps). 1H NMR (400 MHz, CDCl3) δ 1.46 (d, J=6.6 Hz, 3H), 2.51 (d, J=3.0 Hz, 3H), 4.10 (s, 1H), 4.79-4.87 (m, 111), 7.08 (dd, J=8.5, 3.7 Hz, 1H), 7.31 (t, J=8.7 Hz, 1H).

Provenance & Evidence