Potassium ethyl malonate → (4R,5R)-4,5-Dimethyl-3-oxo-heptanoic Acid Ethyl Ester

Participants

Reaction Conditions

Reaction Steps

To a 1 L round bottom flask equipped with a nitrogen inlet was charged 22 g (230 mmol) of magnesium chloride, 39 g (230 mmol) of potassium ethyl malonate and 200 mL of dimethylformamide. The contents of the flask were stirred at 50° C. for 1 hour and then cooled to 35° C. In a separate 500 mL, nitrogen inerted flask was added 200 mL of dimethylformamide, 28.6 g (177 mmol) of carbonyl diimidazole and 20 g of (2R,3R)-2,3-dimethyl-pentanoic acid was dripped in over 30 minutes. When the gas evolution had ceased, the contents of the 500 mL flask were added to the 1 L flask. The reaction was stirred for 2 days at 35° C. The reaction was cooled to room temperature and diluted with 800 mL of 1N HCl. The aqueous solution was extracted 3× with 1 L aliquots of MTBE. The organic extracts were combined and extracted with 200 mL of saturated NaHCO3. The organic layer was dried over MgSO4 and concentrated to give 31.74 g of the titled compound: 1H-NMR (CDCl3) 4.180-4.120 (m, 2H), 3.454 (s, 2H), 2.522-2.453 (q, 1H, J=7.018), 1.738-1.673 (m, 1H), 1.418-1.328 (m, 1H), 1.270-1.217 (m, 3H), 1.113-1.010 (m, 4H), 0.889-0.815 (m, 5H); MS (Ion Mode: APCI) m/z=201 [M+1]+.

Provenance & Evidence