L-Tartaric acid → (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate

Participants

Reaction Steps

To a solution of L-tartaric acid (2.52 g) in THF (12 mL) at 35° C. was added (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione(−)-O,O′-dibenzoyl-L-tartrate (2.0 g, d.e. >99%) to give a suspension which was allowed to cool to ambient temperature. After 90 min, the solid was collected by filtration, washed with 15 mL of THF at 0° C. and dried under vacuum to give (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate which contained 0.5 eq THF by NMR analysis (2.06 g). This product (1.0 g) was added to a solution of L-tartaric acid (1.11 g) in MeOH (10 mL) at reflux and then allowed to cool to ambient temperature with seed crystals of (5R)-5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione L-tartrate (˜5 mg). The solid was collected by filtration, washed with 2×5 ml MeOH at 0° C. and dried under vacuum. (Method 14) 99.25%, Rt 16.22 min.; 0.75%, Rt 18.47 min.; d.e. 98.5%. (Method 2) Rt 2.87 min m/z 357 [M-C4H6O4+]. 1H NMR (400 MHz, DMSO-d6): δ 1.17 (3 H, t, J 7.4), 2.58 (2H, q, J 8.0), 3.04 (1H, dd, J 5.5, 14.2), 3.12 (2H, t, J 6.8), 3.29 (1H, dd, J 4.3, 14.2), 4.27-4.34 (4H, m), 4.86 (1H, dd, J 4.4, 9.1), 6.86 (2H, d, J 8.6), 7.13 (2H, d, J 8.6), 7.26 (1H, d, J 7.8), 7.57 (1H, dd, J 2.6, 8.3), 8.35-8.37 (1H, m).

Provenance & Evidence