Water → Methyl 4-(4-hydroxy-3,5-diisopropylphenyl)-4-oxobutanoate

Participants

Reaction Conditions

Reaction Steps

Propofol 5 (1.78 g, 10.0 mmol) and methyl 4-chloro-4-oxobutyrate (4.5 g, 25 mmol) were dissolved in methylene chloride (350 mL), the reaction mixture was cooled to −78° C. and titanium (IV) chloride (5.7 g, 30 mmol) was added drop-wise. The reaction mixture was stirred for 2 h at −78° C., allowed to warm up to room temperature and stirred overnight. The reaction mixture was then poured into water (300 mL), the organic phase was washed sequentially with saturated sodium bicarbonate solution, water and brine, and the solution dried over anhydrous magnesium sulfate. The product was purified by column chromatography on silica gel using hexane and hexane-ethyl acetate (4:1) step-gradient as an eluent to produce pure 6 (1.14 g, 39%) as a slightly yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.75 (s, 2H), 5.84 (s, 1H), 3.72 (s, 3H), 3.32 (t, J=6.8 Hz, 2H), 3.20 (septet, J=6.9 Hz, 2H), 2.76 (t, J=6.8 Hz, 2H), 1.28 (d, J=6.9 Hz, 12H). 13C NMR (100.61 MHz, CDCl3): δ 196.81, 173.35, 154.40, 133.27, 129.05, 123.97, 51.41, 32.59, 27.82, 26.79, 22.18. HRMS (m/z): [M+H]+ calcd. for C17H24O5 293.1747. found 293.1759.

Provenance & Evidence