Allyl iodide → 2-Allyl-3-methyl-3-phenylbutanoic acid

Participants

Reaction Steps

In accordance with a modified literature procedure (Pfeffer, P. E.; Silbert, L. S.; Chirinko, J. M. J. Org. Chem. 37(3), 1972, 451-458), a solution of 3,3-dimethyl-3-phenyl propionic acid (0.50 g, 2.8 mmol, from Reference Example 22) in tetrahydrofuran (5 mL) is cooled to −40° C. (dry ice/acetone) while stirring under a nitrogen atmosphere. Lithium diisopropylamide (Aldrich, 2.0 M solution in tetrahydrofuran/ethylbenzene/heptane, 3.1 mL, 6.2 mmol) is added dropwise via syringe, followed by 1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H)-pyrimidinone (DMPU, 0.37 mL, 4.2 mmol). The reaction mixture is then allowed to warm to room temperature and to stir for 30 minutes before being re-cooled to 0° C. (ice water bath). Allyl iodide (0.15 mL, 1.3 mmol) is then added neat via syringe and the reaction mixture is allowed to stir overnight while warming to room temperature. The reaction is quenched by the addition of 10% aqueous hydrochloric acid solution and extracted thrice with ethyl acetate. The combined extracts are washed twice with 10% aqueous hydrochloric acid solution and once with saturated sodium chloride solution, dried over anhydrous sodium sulfite, and concentrated under reduced pressure. Flash chromatography (silica gel, hexane/dichloromethane/ethyl acetate) is performed to give a clear blond oil (0.39 g, 64%). MS (ES−): (M−H)=217.0

Provenance & Evidence