Hydrochloric Acid → 3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]-propionic acid

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Reaction Steps

To a solution of trifluoromethanesulfonic acid-2,2,2-trifluoro-1(R)-(4-fluorophenyl)ethyl ester (0.511 g, 88% pure, 1.38 mmol) in CH2Cl2 (5 mL) at rt was added DIPEA (Aldrich, 0.74 mL, 4.24 mmol) followed by the solid HCl salt of 2(R)-amino-3-(morpholin-4-sulfonyl)-propionic acid (0.292 g, 1.06 mmol) in small portions over 2 min. The initially homogeneous orange-brown solution became heterogeneous within minutes and was allowed to stir overnight at rt. The reaction mixture was then diluted with Et2O and quenched with 1M NaOH. The pH 14 aqueous layer was separated, washed with Et2O and acidified to pH 2 with 12M HCl. The aqueous layer was then extracted with Et2O. The combined Et2O extractions of the acidic solution were washed with brine and dried over anhydrous Na2SO4. Following concentration in vacuo, 0.034 g (7.7%) of 3-(morpholin-4-sulfonyl)-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)-ethylamino]propionic acid was obtained as a colorless film.

Provenance & Evidence