Sodium hydride → 2-Chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine

Participants

Reaction Steps

Anhydrous DMF (150 mL) was added to 60% NaH in mineral oil (2.72 g, 67.9 mmol) under an Ar atmosphere, cooled in an ice bath, treated portion-wise with a solution of 2-chloropyridin-4-ol (8 g, 61.8 mmol) in DMF (30 mL) and stirred cold for 5 minutes. The cooling bath was removed and the mixture was warmed to RT and stirred for 20 minutes. 1,2,4-Trifluoro-5-nitrobenzene (13.12 g, 74.1 mmol) was added and the reaction mixture heated at 90° C. for 3 h. The reaction mixture was cooled to RT, concentrated to dryness, treated with EtOH (50 mL) and MeOH (20 mL), warmed gently, then cooled to RT. The yellow solid was collected by filtration, rinsed with EtOH (50 mL) and hexanes (20 mL) and dried under vacuum overnight to provide 2-chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine as a yellow solid (11.68 g, 63% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.48 (dd, J=10.2, 7.0 Hz, 1H), 8.41 (d, J=5.6 Hz, 1H), 7.90 (dd, J=11.6, 6.7 Hz, 1H), 7.41 (d, J=2.1 Hz, 1H), 7.26 (dd, J=5.6, 2.4 Hz, 1H); MS (ESI): m/z 287.0 [M+H]+

Provenance & Evidence