Sodium Diformylamide → 1-Amino-3-[3-(trifluoromethyl)phenyl]acetone hydrochloride

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Reaction Steps

Under argon and with ice cooling, 1.13 g (11.8 mmol) of diformylamide sodium salt were added a little at a time to a solution of 2.67 g (11.2 mmol) of 1-chloro-3-[3-(trifluoromethyl)phenyl]propan-2-one in 11 ml of DMF. The mixture was stirred in an ice bath for 1 h and then at RT overnight. The mixture was then diluted with 25 ml of ethyl acetate and washed successively with in each case 15 ml of 0.5 N hydrochloric acid, water, saturated sodium bicarbonate solution and once more with water. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The dark oily residue was pre-purified on a short silica gel column (mobile phase: dichloromethane/ethanol 95:5). This gave 2.0 g of a dark-brown solid. This was taken up in 25 ml of a 7 N solution of hydrogen chloride in isopropanol, and the mixture was stirred overnight. The solvent was removed under reduced pressure on a rotary evaporator, and the residue was dissolved in about 15 ml of methanol. 100 ml of diethyl ether were stirred into this solution, and the precipitated solid was isolated by filtration. The filter cake was washed with about 10 ml of diisopropyl ether and dried under high vacuum. This gave 0.79 g (28% of theory) of the target compound as a brown solid.

Provenance & Evidence