Hydrochloric Acid → 2-(cis-3-Methoxy-cyclohexyloxy)-3-nitro-pyridine

Participants

Reaction Steps

LiHMDS (1 M solution in THF; 40.0 ml) was added slowly to an ice/ethanol-cooled solution of cis/trans-4-methoxy-cyclohexanol (5.00 g) in THF (10 ml). Cooling was suspended after the addition was complete and the mixture was stirred for 15 minutes at room temperature. A solution of 2-fluoro-3-nitro-pyridine (5.10 g) in THF (10 ml) was added slowly while the temperature was maintained below 24° C. The reaction mixture was stirred for 2 h at room temperature, neutralized by addition of hydrochloric acid (1M), and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was submitted to column chromatography (silica gel, petrol ether/ethyl acetate 70:30 50:50) to give the cis-isomer (5.82 g) and the trans-isomer (1.60 g).

Provenance & Evidence