ETHYL 3-(TETRAHYDROFURAN-3-YL)-3-OXOPROPANOATE synthesis

Yield:-

Reaction Conditions:

Stage #1:ethyl acetate with lithium hexamethyldisilazane in tetrahydrofuran;hexanes at -78; for 0.5 h;
Stage #2:methyl tetrahydrofuran-3-carboxylate in tetrahydrofuran;hexanes at -78; for 4 h;

Steps:

4
Intermediate 4: 3-Oxo-3-(tetrahydro-furan-3-yl)-propionic acid ethyl ester To a solution of lithium bis(trimethylsilyl)amide (1 M in hexanes; 100 mL) in THF (200 mL) at -78° C. was added dry ethyl acetate (10.8 g, 12 mL, 122.5 mmol) dropwise. After 30 min at -78° C., the mixture was treated with a solution of tetrahydro-furan-3-carboxylic acid methyl ester (6.0 g, 46.1 mmol) in THF (50 mL). After 4 h at -78° C., the reaction was quenched with satd. aq. NH₄Cl, warmed to rt, and extracted with EtOAc (5*75 mL). The combined organic layers were washed with satd. aq. NaCl, dried, and concentrated to give a colorless oil. Chromatography on SiO₂ (EtOAc/CH₂Cl₂) afforded the title compound (3.3 g).

References:

Cai, Hui;Chavez, Frank;Edwards, James P.;Fitzgerald, Anne E.;Liu, Jing;Mani, Neelakandha S.;Neff, Danielle K.;Rizzolio, Michele C.;Savall, Brad M.;Smith, Deborah M.;Venable, Jennifer D.;Wei, Jianmei;Wolin, Ronald L. US2008/194577, 2008, A1 Location in patent:Page/Page column 26