A Simple and Convenient Synthesis of Triprolidine
171
conc. ammonia solution. The solid product was extracted into hexane (3 × 150 mL) and the
hexane layer was dried over anhydrous sodium sulfate and evaporated to afford triprolidine
(35 g, 87% yield). The free base thus obtained was dissolved in 175 mL of 2-butanone,
12 g of oxalic acid was added and then the mixture was stirred at room temperature for 2
hours. The solid product obtained was collected and dried to yield the E-isomer (99% pure
by HPLC, 38.0 g, 75% yield). The pure E-isomer of triprolidine oxalate was dissolved in
100 mL of water and 7 mL of conc. ammonia was added to yield triprolidine free base as a
solid (28 g). The solid obtained was dissolved in 150 mL of ethyl acetate, and 10% gaseous
HCl in isopropanol (37 mL) was added to afford triprolidine hydrochloride (29.0 g, 67%
yield) as a white solid, mp. 117–118◦C, lit.18 mp.116–118◦C.
IR(KBr): 3402, 3251, 2885, 2611, 2499, 1631, 1581, 1512, 1461, 1427, 991 cm−1. 1H
NMR (D2O, 200 MHz): δ 2.05 (brs, 4 H), 2.43 (s, 3 H), 3.34 (brs, 4 H), 3.97 (d, 2 H, J =
7.2 Hz), 6.55 (t, 1 H, J = 7.2 Hz), 7.13 (d, 2 H, J = 7.8 Hz), 7.25 (d, 1 H, J = 7.8 Hz), 7.37
(d, 2 H, J = 7.8 Hz), 7.43 (m, 1 H), 7.80 (t, 1 H, J = 7.8 Hz), 8.53 (d, 1 H, J = 4.4 Hz). 13C
NMR (CDCl3, 50 MHz) δ 21.1, 23.3, 52.3, 119.0, 123.0, 129.1, 129.6, 133.1, 136.5, 138.3,
148.1, 149.2, 156.2; TOF-MS (ES+) m/z: 279(M+H)+, 208 (100%).
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