7-METHYL-2,4-OCTANEDIONE synthesis

Yield:999-05-3 71%

Reaction Conditions:

Stage #1: acetic acid methyl esterwith sodium hydride in diethyl ether;mineral oil;Reflux;Claisen Condensation;
Stage #2: 5-Methyl-2-hexanone in diethyl ether;mineral oil; for 8 h;

Steps:

1

7-Methyl-2,4-octanedione (13)To a stirred solution of methyl acetate 11 (27.8 ml; 25.9 g; 350 mmol) in diethyl ether (200 ml) sodium hydride (60% w/w; 4.8 g; 200 mmol) was added and the resultant slurry was brought to reflux. Then a solution of 5-methyl-2-hexanone 12 (24.6 ml; 20.0 g; 175 mmol) in diethyl ether (150 ml) was added dropwise over 3 hours. Refluxing was maintained for next 5 hours. Then 10% aqueous solution of HCl with crushed ice (ca. 100 ml) was added carefully and the organic phase was separated. The aqueous phase was extracted with diethyl ether (150 ml) and the combined organic phases were washed with saturated aqueous solution of NaHCO₃ (50 ml), dried over anhydrous MgSO₄ and concentrated under reduced pressure. The residue was purified by distillation under reduced pressure to give 19.5 g (125 mmol; 71% yield) of 13. ¹H NMR (400 MHz, CDCl₃) δ 0.88-0.92 (6H, m), 1.49 (2H, m), 1.57 (1H, m), 2.05 (2.6H, s), 2.13 (0.1H, s), 2.18 (0.2H, s), 2.24-2.29 (2H, m), 2.51 (0.3H, t, J=7.5 Hz), 3.58 (0.3H, s), 5.50 (0.6H, s); ¹³C NMR (100 MHz, CDCl₃) δ 22.3, 24.9, 27.5, 27.7, 30.9, 32.1, 34.6, 36.3, 44.7, 57.9, 99.7, 191.3, 194.7; exact mass (ESI) calculated for C₉H₁₆O₂Na ([M+Na]⁺) 179.1048. found 179.1040.

References:

US2012/309719,2012,A1 Location in patent:Page/Page column 15