Hydrochloric Acid → HCID 88897924, compound

Participants

Reaction Conditions

Reaction Steps

A stirred solution of (S)-3-tert-Butoxycarbonylamino-2-[(2-tert-butoxycarbonylamino-4-trifluoromethyl-thiazole-5-carbonyl)-amino]-propionic acid methyl ester (10.67 g, 20.82 mmol) in methanol (80 mL) was treated with the 4 M HCl in Dioxane (50 mL, 200 mmol) and reaction was heated at 40° C. for 45 min. The resultant intermediate was concentrated to give a pale yellow foam oil. A solution of this material in DMF (150 mL) was treated with the HBTU (9.6 g, 25.31 mmol), HOBt (3.5 g, 25.90 mmol), 2-thiophenecarboxylic acid (2.9 g, 22.63 mmol) and the triethylamine (19 mL, 136.3 mmol) and stirred at room temp for 2 h. The reaction was then concentrated to remove DMF, followed by dilution with water (300 mL), and extracted with ethyl acetate (1×300 mL, 1×100 mL). The combined organic layers washed with water (3×100 mL) followed by aq sat sodium bicarbonate solution (3×100 mL), water (2×100 mL), brine (100 mL), dried over magnesium sulfate, filtered, concentrated to give (9.41 g) as crude product. Column purification The solid residue was purified by flash column (20-80 EtOAc in hexane) to give 10.2 g (98%) of yellow oil. MS m/e 523.5 (M+H+).

Provenance & Evidence