Methanol → 1-Ethyl-4-methoxy-1,3-dihydro-furo[3,4-c]pyridin-1-ol

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To 10.52 mL triethylaluminum in toluene (1.9 M, 19.99 mmol, 1.1 eq) were added dropwise 39.97 mL ethyllithium in cyclohexane/benzene (0.5 M, 19.99 mmol, 1.1 eq) at 0° C. After 15 min at 0° C., 50.5 mL THF (precooled to −40° C.), were added rapidly via a canula. A solution of 3.0 g 4-methoxy-3H-furo[3,4-c]pyridin-1-one (18.17 mmol), as obtainable from example 15, in 75 mL THF was subsequently added rapidly at 40° C. After 10 min at −40° C., additional 39.97 mL ethyllithium in cyclohexane/benzene (0.5 M, 19.99 mmol, 1.1 eq) were added slowly. The mixture was allowed to warm up to −15° C. within 3 h and the reaction was afterwards quenched by addition of 3.68 mL methanol (100 mmol, 5 eq). After 30 min, the mixture was poured in 1.5 L saturated aqueous potassium sodium tartrate and was extracted three times with 500 mL, in total with 1.5 L dichloromethane. The combined organic phases were dried over 100 g Na2SO4 (30 min) and filtered. The solid was washed with 200 mL dichloromethane. After evaporation of solvent in a rotary evaporator (40° C./10 mbar), the crude product (3.77 g, 106% w/w) was obtained as a brown oil (HPLC purity 51.5% area), which was purified by column chromatography with heptane/ethyl acetate (7:3) yielding the title product (1.877 g, 9.61 mmol, 53% w/w ; HPLC purity 97.9% area; ratio lactol/hydroxy-ketone=6:1 by NMR) as yellow oil.

Herkunft & Nachweise