Bis-PEG2-acid synthesis

Yield: 75%

Reaction Conditions:

with potassium hydroxide in ethanol;water at 85; for 1 h;

Steps:

Step 2: 3,3'-(ethane-1,2-diylbis(oxy))dipropanoic acid (Q).
To a solution of ethyl 3,3'-(ethane-1,2-diylbis(oxy))dipropanoate P (2.3 g, 8.7 mmol)in ethanol/water (40 mL / 2 mL) was added potassium hydroxide (492 mg, 8.7 mmol). Thereaction was stirred at 85 oC for 1 h then was concentrated, diluted with H2O (20 mL), andadjusted to pH = 9 with saturated NaHCO3 solution (10 mL). The mixture was extracted withEtOAc (20 mL × 2) then the aqueous phase was adjusted pH = 3 with 2 M HCl solution andextracted with iPrOH/CCl3 (1:3). The combined organic layers were dried over Na2SO4,filtered, and concentrated to afford the title compound (1.3 g, 75%) as colorless oil.

References:

Dragovich, Peter S.;Adhikari, Pragya;Blake, Robert A.;Blaquiere, Nicole;Chen, Jinhua;Cheng, Yun-Xing;den Besten, Willem;Han, Jinping;Hartman, Steven J.;He, Jintang;He, Mingtao;Rei Ingalla, Ellen;Kamath, Amrita V.;Kleinheinz, Tracy;Lai, Tommy;Leipold, Douglas D.;Li, Chun Sing;Liu, Qi;Lu, Jiawei;Lu, Ying;Meng, Fanwei;Meng, Lingyao;Ng, Carl;Peng, Kaishan;Lewis Phillips, Gail;Pillow, Thomas H.;Rowntree, Rebecca K.;Sadowsky, Jack D.;Sampath, Deepak;Staben, Leanna;Staben, Steven T.;Wai, John;Wan, Kunpeng;Wang, Xinxin;Wei, BinQing;Wertz, Ingrid E.;Xin, Jianfeng;Xu, Keyang;Yao, Hui;Zang, Richard;Zhang, Donglu;Zhou, Hao;Zhao, Yongxin [Bioorganic and Medicinal Chemistry Letters,2020,vol. 30,# 4,art. no. 126907] Location in patent:supporting information