Hydrochloric Acid → 2-(3-(Hydroxymethyl)-6-nitro-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of racemic (7-nitro-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol (1.00 g, 4.73 mmol) and 4-chlorophenoxyacetonitrile (827 mg, 4.94 mmol) in DMF (12 mL) was added dropwise to a solution of potassium tert-butoxide (2.12 g, 18.9 mmol) in DMF (20 mL) at −5-0° C. After the addition was complete (7 minutes), the reaction mixture was stirred for 1 hour at −5-0° C. The reaction mixture was acidified with 1 N HCl before drowning into water (200 mL). The mixture was extracted with EtOAc (3×100 mL) and the combined organic layers were washed with 1N NaOH (3×50 mL) to remove most of the 4-chlorophenol. After removal of solvent, the residue was purified by flash chromatography on silica gel, gradient elution using 2:3, 1:1, 3:2, 100:0 ethyl acetate/hexane, to give 139 mg, 14% recovered starting material and 804 mg, 68% yield of the title compound as a solid. 1H NMR (CDCl3) δ 7.77 (1H, d, J=9.12 Hz); 7.01 (1H, d, J=9.12 Hz); 4.50-4.40 (2H, m); 4.30-3.91 (5H, m); 2.25-2.21 (1H, m). 13C NMR (CDCl3) δ 148.07, 141.71, 141.55, 119.44, 117.07, 116.96, 115.71, 74.36, 65.31, 61.18, 14.89.

Provenance & Evidence