Sulfuric Acid → HCID 136183453, compound

Participants

Reaction Steps

3-Methyladipic acid 1 (1.60 g, 10 mmol) was heated under reflux in ethanol/conc. sulfuric acid solution (35 mL, v/v=2.5/1) for 8 h. The solution was neutralized with ammonium hydroxide to pH=7, then diluted with ethyl acetate (100 mL) and washed with water. The organic phase was dried with anhydrous sodium sulfate and evaporated to afford a light yellow liquid which was used in the next step without further purification. The resulting liquid was diluted in anhydrous toluene (100 mL) and sodium (0.23 g) was added to the solution in part. The mixture was heated under reflux for 3 h and cooled, neutralized with 1N hydrochloric acid solution and washed with water. After drying with anhydrous sodium sulfate, the organic phase was evaporated to afford a light brown liquid. The liquid was used in the next step without further purification. The light brown liquid was diluted with t-BuOH. Acetamidine (1.13 g, 12 mmol) and potassium tert-butoxide (1.34 g, 12 mmol) were added, and the mixture was heated under reflux overnight. The reaction mixture was cooled and the precipitate was filtered. The residue was washed with warm methanol twice (30 mL×1, 15 mL×1). The filtrate and washings were combined and evaporated under reduced pressure, and the residue was purified by column chromatography using chloroform/methanol (100/1) as eluent to afford 345 mg (21% yield total for 3 steps) as a white solid. TLC Rf0.30 (CHCl3/CH3OH, 10:1); mp: 173.9-175.4° C. 1H NMR (DMSO-d6): δ 1.05-1.07 (d, 3 H, CH3), δ 2.24 (s, 3 H, CH3), δ 2.13-2.34, 2.73-2.90 (m, 5 H, CH2CHCH2), δ 12.16 (br, 1H, OH, exch). Anal. (C9H12N2O) C, H, N: calcd, 65.83, 7.37, 17.06; found, 65.85, 7.36, 17.12.

Provenance & Evidence