Hydrochloric Acid → Pioglitazone hydrochloride, (R)-

Participants

Reaction Steps

The product from Example 15, Step 3 was dissolved in MeOH (2.25 mL) containing 37% HCl (0.134 mL) at 35° C. The solution was filtered, EtOAc (9 mL) was poured into the stirred solution and the mixture stirred for 20 min. The white solid was collected by filtration, washed with EtOAc and dried at 30° C. under high vacuum to give the title compound (0.181 g). (Method 1) 98.3%, Rt 10.65 min.; 1.7%, Rt 14.83 min e.e. 96.6%. LCMS (Method 2): Rt 2.90 min 99.39%, m/z 357 [MH+—HCl]. LCMS (Method 3) Rt 2.91 min, m/z 357 [MH+—HCl]. 1H NMR (400 MHz, DMSO-d6): δ 12.0 (1H, s), 8.70 (1H, d, J=1.7 Hz), 8.36 (1H, bd, J=8.3 Hz), 7.93 (1H, d, J=8.2 Hz), 7.15, 6.87 (4H, A2B2q, J=8.7 Hz), 4.86 (1H, dd, J 4.4, 8.9 Hz), 4.38 (2H, t, J=6.3 Hz), 3.44 (2H, t, J=6.2 Hz), 3.29 (1H, dd, J 4.3, 14.2 Hz), 3.06 (1H, dd, J 9.0, 14.3 Hz), 2.78 (2H, q, J=7.6 Hz), 1.23 (3H, t, J=7.6 Hz).

Provenance & Evidence