Dimethylformamide → 4-ethyl-8-methoxy-1H-pyrano[3,4-c]pyridine

Participants

Reaction Conditions

Reaction Steps

A 3-liter 3-necked round-bottom flask is equipped with a heating mantle monitored by a J-KEM thermocouple and an overhead stirrer; under nitrogen, the flask is charged with 3-(but-2-enyloxymethyl)-4-iodo-2-methoxy-pyridine (30.0 g, 93.9 mmol), as prepared in example 2, and 939 mL (0.1M) of N,N-dimethylformamide, followed by successive addition of anhydrous potassium carbonate (26.0 g, 188 mmol), palladium(II) acetate (422 mg, 1.88 mmol) and tetrabutylammonium chloride (13.1 g, 47.0 mmol). The light brown mixture is brought to 90° C. and stirred for 30 min. The now dark brown mixture is allowed to cool to 85° C. and stirring is continued for 20 h when TLC (10% EtOAc/hexane) indicates complete reaction. After being cooled to ambient temperature, the mixture is filtered through Celite 545® (80 g), washed with MTBE (0.5 L) and the filtrate is poured into 800 mL of ice water and extracted with MTBE (3×600 mL). The combined extracts are successively washed with water (700 mL) and brine (700 mL), dried over anhydrous Na2SO4 (150 g). Evaporation in vacuo yields crude 4-ethyl-8-methoxy-1H-pyrano[3,4-c]pyridine 1H NMR (400 MHz) indicates an endo/exo ratio of 8:1. Vacuum distillation at, ca. 112°-120° C. yields 4-ethyl-8-methoxy-1H-pyrano[3,4-c]pyridine as an 11:1 endo/exo mixture. 1H-NMR (400 MHz, CDCl3) δ8.04 (d, J=5.4 Hz, 1H), 6.65 (d, J=5.4 Hz, 1H), 6.54 (s, 1H), 5.04 (s, 2H), 3.94 (s, 3H), 2.32 (m, 2H), 0.97 (t, J=7.2 Hz, 3H), HRMS (EI+): calc for C11H13NO2 : 191.0946, Found: 191.0952. IR 3450, 2962, 1731, 1602, 1581, 1454, 1390, 1362, 1313, 1267 cm-1

Provenance & Evidence