Dimethylformamide → 2-(1,1-Dimethylethyl)-1,2,3,4-tetrahydro-6-methoxy-2,7-naphthyridine

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Reaction Conditions

Reaction Steps

To a stirred solution of 2,2,6,6-tetramethylpiperidine (9.0 mL, 60 mmol) in dry THF (300 mL) under argon at −20° C. was slowly added 1.6M n-BuLi in hexanes (40 mL, 60 mmol) while the temperature was kept at −20° C. After the addition was complete, stirring was continued at −20° C. for 40 min. Then a solution of tert-butyl-[(6-methoxy-4-methylpyridin-3-yl)methylene]amine (6.3 g, 30 mmol) in dry THF (100 mL) was added dropwise at −20° C. The mixture was stirred at −15 to −10° C. for 1.5 h and then cooled to −20° C. Anhydrous DMF (6.5 ml, 70 mmol) was added dropwise over five minutes and stirring continued at −10° C. for 1.5 h. Then glacial acetic acid (60 mL) in MeOH (250 ml) was added, followed by the portion-wise addition of sodium cyanoborohydride (2.3 g, 40 mmol) over five minutes. After stirring overnight, the solvent was evaporated and 20% potassium carbonate solution was added slowly to raise the pH to 9. The mixture was extracted four times with TBME. The combined organic phases were washed with brine, dried and concentrated to give a crude oil. Vacuum distillation gave 5.2 g (77%) of the title compound as a colourless oil, b.p. 105-106° C./0.5 mmHg.

Provenance & Evidence