Hydrochloric Acid → HCID 18701603, compound

Participants

Reaction Steps

Magnesium (1.34 g, 55 mmol) was suspended in THF (300 mL) and a solution of 4-bromothioanisole (10.16 g, 50 mmol) in THF (50 mL) was added dropwise over 0.5 hour maintaining the temperature at less than 30° C. The reaction was stirred an additional 0.5 hour once the addition was complete. 3-Fluoro-p-anisaldehyde silyl cyanohydrin (Example 34, Step 1) (12.7 g, 50 mmol) and diethyl ether (50 mL) were added dropwise to the solution of Grignard at such a rate that the reaction temperature did not rise above 30° C. Upon complete addition, the reaction was stirred an additional 15 minutes at which time 1N HCl (400 mL) was added and the reaction stirred until all solids were dissolved. The organics were washed with NaHCO3 (saturated) (400 mL) and brine (400 mL), dried over Na2SO4 and concentrated to yield a mixture of benzoin and silyl benzoin. The crude product was dissolved in TFA/H2O (9:1) (75 mL) and stirred for 15 minutes. The TFA solution was poured into saturated NaHCO3 (aq.). The benzoin was extracted with ethyl acetate (350 mL) and washed with NaHCO3 (saturated) (300 mL) and brine (300 mL). The crude benzoin was crystallized from ethyl acetate and hexane to yield crystals of 4-methylthio-3'-fluoro-4'-methoxybenzoin (4.9 g, 32%): 1H NMR (CDCl3) 300 MHz δ 2.45 (s, 3H), 3.81 (s, 3H), 5.8 (s, 1H), 6.86 (m, 1H), 7.01 (m, 2H), 7.17 (d, J=8.7 Hz, 2H), 7.79 (d, J=8.7 Hz, 2H); 19F NMR (CDCl3) 282 MHz δ -134.0 (multiplet).

Provenance & Evidence