Tetrahydrofuran → Ethyl 3-bromo-4-cyano-5-[2-(hydroxymethyl)morpholin-4-yl]thiophene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Ethyl 3,5-dibromo-4-cyanothiophene-2-carboxylate (0.360 g, 1.06 mmol), cesium carbonate (1.05 g, 3.21 mmol), 2-hydroxymethylmorpholine (137 mg, 1.17 mmol), and tetrahydrofuran (4.5 mL, 36 mmol) were combined in a 15 mL pressure vessel equipped with a stir bar. The vessel was sealed, and the r×n was heated @ 90° C. with stirring for 4 hours. The reaction was cooled to rt. The r×n was poured into water/saline. The reaction vessel was washed out with additional water, then ethyl acetate, and these were added to the quench which was then transferred to a separatory funnel. The aqueous layer was extracted 3× with EtOAc. The extracts were combined, washed with saline, dried over Na2SO4, filtered, added Celite, concentrated in vacuo, and dried on high vac 30 min. Purified dry load via silica gel chromatography (gradient elution: 0-60% EtOAc/hexanes) to give 163 mg solid (41% yield). 1H NMR (400 MHz, DMSO) δ 4.91 (t, J=5.7 Hz, 1H), 4.25 (q, J=7.1 Hz, 2H), 3.99-3.92 (m, 3H), 3.69-3.58 (m, 2H), 3.50 (dt, J=10.5, 5.2 Hz, 1H), 3.41 (dt, J=11.5, 5.8 Hz, 1H), 3.37-3.27 (m, 1H, under H2O peak), 3.15-3.08 (m, 1H), 1.26 (t, J=7.1 Hz, 3H).

Provenance & Evidence