Hydrochloric Acid → Atomoxetine impurity D CRS

Participants

Reaction Steps

Under stirring, while maintaining the temperature between about 15° and about 25° C. with an ice-water bath, 8.55 g of 36% aqueous hydrogen chloride are dropped on the filtered organic phase, resulting in the crystallization and suspension of the 3-ATM Hydrochloride (mw 291.82). The suspension is stirred at about 20° C. for 1 hour, the solid is collected by filtration, washed twice with 35 ml of n-butyl acetate, and dried for 18 hours under vacuum at about 50° to about 60° C., yielding about 19.6 g of product, having a melting point of about 159° to about 160° C., and 1H-NMR data of 9.58 ppm, bs, 2H, 7.35-7.20 ppm, m, 5H, 7.01 ppm, t, 1H; 6.68-6.65 ppm, m, 2H, 6.59 ppm, dd, 1H, 5.30 ppm, dd, 1H; 3.10 ppm, quint, 2H; 2.57 ppm, t, 3H, 2.41 ppm, m, 2H, 2.22 ppm, s, 3H. The yield is 28 percent by weight based on the starting N-methyl-3-hydroxy-3-phenylpropylamine. The 3-ATM HCl is determined to be a mixture of enantiomers, with relative ratio: 99/1 by chiral HPLC.

Provenance & Evidence