Hydrochloric Acid → (R)-ethyl 3-amino-4-(2',5'-dichlorobiphenyl-4-yl)butanoate hydrochloride

참여 물질

반응 단계

To (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(2′,5′-dichlorobiphenyl-4-yl)butanoate (1.09 g, 2.33 mmol) is added a solution of 4 M HCl in 1,4-dioxane (5.81 mL, 23.3 mmol) at room temperature. After stirring for 2 hours, the reaction mixture is concentrated under reduced pressure to give (R)-ethyl 3-amino-4-(2′,5′-dichlorobiphenyl-4-yl)butanoate hydrochloride. Next, a solution of the product, succinic anhydride (280 mg, 2.80 mmol) and DIPEA (0.489 mL, 2.80 mmol) in dichloromethane (15 mL) is allowed to stir for 2 hours. The reaction is quenched with 1 M aqueous HCl and extracted with dichloromethane. The organic layer is separated and concentrated under reduced pressure. The resulting residue is purified by preparative HPLC using a gradient of 20% MeCN/water (0.1% TFA) to 100% MeCN to give (R)-4-(1-(2′,5′-dichlorobiphenyl-4-yl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid (553 mg) as a white solid; HPLC retention time=1.02 minutes (condition B); MS (m+1)=452.14; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (t, J=7.2 Hz, 3 H) 2.47-2.67 (m, 6 H) 2.89 (A of ABX, Jab=13.7 Hz, Jax=7.8 Hz, 1 H) 3.00 (B of ABX, Jab=13.7 Hz, Jbx=6.7 Hz, 1 H) 4.12-4.24 (m, 2 H) 4.49-4.57 (m, 1 H) 6.53 (br d, J=8.8 Hz, 1 H) 7.23-7.26 (m, 3 H) 7.32-7.40 (m, 4 H).

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