Acetone → 4-Fluoro-alpha-(1-hydroxy-1-methylethyl)benzeneacetic acid

Participants

Reaction Steps

24.3 g (1.00 mol) of magnesium shavings were suspended in 50 ml of tetrahydrofuran under argon and while stirring in a 1.5 l four-necked sulphonation flask fitted with a reflux condenser, mechanical stirrer, 500 ml dropping funnel, thermometer and a device for inert gasification. After the dropwise addition of 0.5 ml of 1,2-dibromoethane, a solution of 86.4 g (1.10 mol) of isopropyl chloride in 225 ml of tetrahydrofuran was added dropwise within 90 minutes, with the reaction temperature being held at about 30°. The resulting dark grey suspension was stirred at RT for a further 18 hours. Then, a solution of 73.0 g (0.473 mol) of p-fluorophenylacetic acid in 150 ml of tetrahydrofuran was added dropwise to the mixture within 90 minutes while maintaining the temperature at about 25° and thereafter the suspension was heated to 35-40° and stirred at this temperature for a further 1 hour. After cooling 30.0 g (0.516 mol) of acetone were added dropwise at about 25° within 30 minutes and subsequently the mixture was stirred at 35-40° for a further 1 hour. The reaction mixture was treated with 350 ml of 14.2% sulphuric acid while cooling with an ice bath at <30°. The aqueous phase was separated, extracted with 200 ml of tetrahydrofuran and the organic phases were combined and evaporated at 50° on a rotary evaporator. 110 g of crude 2-(p-fluorophenyl)-3-hydroxy-3-methylbutyric acid were obtained as a dark viscous oil.

Provenance & Evidence