Acetone → 2-(1-Hydroxy-1-methyl-ethyl)-2-methyl-but-3-enoic acid

Participants

Reaction Conditions

Reaction Steps

A cooled (−78° C.) solution of N,N-diisopropylamine (12.5 g, 123 mmol) in anhydrous tetrahydrofuran (100 mL) was treated with n-butyllithium (2.5 M solution in hexanes, 49 mL, 123 mmol). Temperature was raised to 0° C. for 30 minutes, then re-cooled down to −78° C. Tiglic acid (5.00 g, 49.4 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise. Temperature was raised to room temperature for 1 h then re-cooled down to −78° C. Acetone (2.86 g, 49.4 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise. After stirring for 3 h, the reaction was quenched with a saturated solution of ammonium chloride and allowed to warm up to room temperature. The pH was adjusted to pH 2 by addition of concentrated hydrochloric acid and diethyl ether (400 mL) was added. The organic layer was separated, and the volatiles removed in vacuo. The residue was partitioned between diethyl ether (200 mL) and a saturated solution of sodium bicarbonate (300 mL). The aqueous layer was acidified to pH 1 with concentrated hydrochloric acid, then re-extracted with diethyl ether (2×100 mL). The organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/acetone 1:0 to 3:2 to afford the title compound (5.129 g, 66%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 1.27 (s, 3H), 1.31 (s, 3H), 1.38 (s, 3H), 5.28 (d, J=17.6 Hz, 1H), 5.34 (d, J=10.9 Hz, 1H), 6.25 (dd, J=17.6, 10.9 Hz, 1H).

Provenance & Evidence