Lithium Hydroxide → KD-3010

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid methyl ester, in THF, is added a solution of lithium hydroxide in water, which is stirred at 20° C. and concentrated under reduced pressure. The reaction mixture is cooled to 9° C., neutralized with 32% HCl, and extracted from toluene. Water is removed from the organic solution by azeotropic distillation. Following distillation, the organic solution is cooled to ambient temperature and transferred to a feeding vessel. The reactor is charged with p-toluenesulfonic acid in toluene and water is removed by azeotropic distillation. The solution is cooled to 60° C., followed by the addition of the organic solution from the feeding vessel. The mixture is stirred at 83° C., then cooled to 10° C. to induce crystallization. The product suspension is filtered, the filter cake rinsed with heptane, and dried on a rotovap, at 40° C., to afford (S)-4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid tosylate. 1HNMR δ 1.60 (d), 1.62 (d), 2.33 (s), 3.23 (m), 3.49 (m), 3.39 (m), 4.05 (m), 4.49 (m), 3.40 (dd), 3.23 (dd), 7.14 (d), 7.14 (d), 7.09 (d), 7.09 (d), 7.59 (d), 7.59 (d), 7.71 (d), 7.26, dd, 7.57 (d), 7.57 (d), 7.40 (d).

Provenance & Evidence