Trifluoroacetic acid → 3-Bromo-2,5-dimethyl-4-{[4-(trifluoromethyl)phenyl]methyl}thiophene

Participants

Reaction Steps

To a solution of (4-bromo-2,5-dimethyl-3-thienyl)[4-(trifluoromethyl)phenyl]methanol (74.0 g, 200 mmol) Example 11, Step 2 and triethylsilane (130 mL, 800 mmol) in 500 mL of dichloromethane at 0° C. under nitrogen is added trifluoroacetic acid (155 mL, 2.00 mol) such as to maintain an internal temperature between 1 and 4.5° C. Most of the volatiles are removed under reduced pressure and the resulting solution poured onto ether (1 L) and a mixture of sat. aq. sodium bicarbonate and water (500 mL). The phases are separated. The organic layer is washed with brine (200 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue is diluted and concentrated twice from toluene (300 mL). The residue is split in two equal parts, diluted with hexanes (each part with 30 mL) and each part is applied onto 330 g silica gel columns for purification with Combi Flash chromatography system (100% hexanes for 5 minutes then going to 5% ethyl acetate/95% hexanes over 21 minutes to afford the desired product as a colorless liquid.

Provenance & Evidence