Citric Acid → 4-METHYLTETRAHYDRO-2H-PYRAN-4-CARBOXYLIC ACID

Participants

Reaction Conditions

Reaction Steps

Diisopropylamine (6.37 mL, 44.7 mmol) in THF (50 mL) was cooled to 0° C. under argon. N-Butyllithium (16.7 mL, 2.5 M in hexane, 41.7 mmol) was added dropwise over 10 min. The reaction mixture was left to stir for 15 min at 0° C. A solution of tetrahydro-2H-pyran-4-carboxylic acid (D8) (1.94 g, 14.9 mmol) in THF (10 mL) was added and a white precipitate was formed. The resulting mixture was then heated at 50° C. for 3 h. The reaction mixture was cooled to 0° C. and methyl iodide (2.80 mL, 44.7 mmol) was added dropwise. The reaction was then allowed to warm to rt and left to stir overnight. 10% aqueous citric acid solution (40 mL) was then added and the THF was removed by rotary evaporation. The residual aqueous mixture was extracted with Et2O (2×). The organics were combined, dried (Na2SO4) and concentrated by rotary evaporation to give the title compound (D9) (1.26 g, 53%) as a yellow solid.

Provenance & Evidence