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), prepared as 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 acetate (422 mg, 1.88 mmol) and tetra-n-butylammonium 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 about 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 C11H13 NO2 : 191.0946, Found: 191.0952. IR 3450, 2962, 1731, 1602, 1581, 1454, 1390, 1362, 1313, 1267 cm-1

Provenance & Evidence