(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol

30071-93-3

7480-35-5

368-63-8

The general procedure for the synthesis of 1-[3,5-bis(trifluoromethyl)phenyl]ethanol from 3,5-bis(trifluoromethyl)phenylacetophenone and cis-1-amino-2,3-dihydro-1H-inden-2-ol was as follows: in Example 5, [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)- cis-1-amino-2-inden-2-ol (9.0 g) and 1- (3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) were dissolved in 2-propanol (21 L), stirred for 30 min and thoroughly degassed under vacuum. A 5M sodium hydroxide solution (28mL) was then added and the mixture was aged for 4-6 hours to ensure complete conversion of the feedstock. Upon completion of the reaction, the mixture was poured into 1N HCl (21L) and extracted with heptane (2 x 10.5L). The organic layers were combined, washed with brine, and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to nearly 4 mL/g of alcohol (KF < 200 μg/mL; 2-propanol < 5 vol%). The mixture was inoculated at 40°C and allowed to cool slowly to room temperature to form crystalline species, which were then further cooled to 0°C. The crystalline product was collected by filtration, washed with cold heptane and dried to give the DABCO complex in 75-80% yield and ee value >99%.