Sodium hydride → HCID 18391695, compound

Participants

Reaction Steps

To an ice cooled solution of the compound of step 7b (941 mg, 5.0 mmol) in tetrahydrofuran (30 mL) under nitrogen, was added sodium hydride (80% dispersion in mineral oil, 180 mg, 7.5 mmol), portionwise. The reaction mixture stirred fifteen minutes followed by the dropwise addition of 2-chloropyrazine (590 mg, 5.1 mmol). The reaction was stirred 24 hours gradually warming to room temperature. Additional sodium hydride (40 mg) was added and stirring at room temperature continued until complete disappearance of starting material by TLC. The reaction mixture was then treated with a 10% aqueous solution of potassium hydrogen sulfate (20 ml) and the volatiles evaporated in vacuo. The mixture was then diluted with ethyl acetate (50 ml) and the organic phase was washed with saturated sodium hydrogen carbonate (2×20 ml). The organic phase was then dried (MgSO4), filtered and concentrated in vacuo. The resultant orange oil (1.37 g) was purified by flash silica gel chromatography (ethyl acetate:hexane=1:1), resulting in product isolated as an oil, in 80% yield (1.07 g). [α]23D =-62.8° (c 1.35, CHCl3). MS (CI/NH3) m/e 266 (M+H)+, 283 (M+NH4)+. 1H NMR (CDCl3, 300 MHz) δ: 8.28-8.27 (d, J=1.1 Hz, 1H), 8.13-8.12 (d, J=2.58 Hz, 1H), 8.08-8.06 (dd, J=2.58, J=1.5 Hz, 1H), 4.66-4.61 (dd, J=10.83, J=4.6, 1H), 4.58-4.51 (m, 1H), 4.50-4.45 (dd, J=10.83, J=3.13, 1H, 3.92-3.87 (dd, J=8.3, J=6.25, 2H), 2.41-2.29 (m, 1H), 2.26-2.16 (m, 1H), 1.41 (s, 9H).

Provenance & Evidence