Water → 4-(3-Fluoro-5-nitro-phenoxy)-1-methyl-piperidine

Participants

Reaction Conditions

Reaction Steps

Dissolve 1-methyl-piperidin-4-ol (3.62 g, 31.43 mmol) in N,N-dimethylformamide (20 mL) and add 95% sodium hydride (0.83 g, 33.0 mmol) at ambient temperature. After 40 min., add 1,3-difluoro-5-nitro-benzene (5.0 g, 31.43 mmol), stir and heat at 65° C. After 2 hr., cool to ambient temperature and pour slowly into water (100 mL). Extract the reaction mixture with ethyl acetate (3×150 mL), wash the combined organic layers with aqueous NaCl solution (100 mL), dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride to obtain of the title compound (2.76 g, 35%). 1H NMR (CDCl3): 7.6 (s, 1H), 7.5 (d, 1H), 7.0 (d, 1H), 4.4 (m, 1H), 2.7 (m, 2H), 2.4 (m, 5H), 2.0 (m, 2H), 1.9 (m, 2H).

Provenance & Evidence