With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.4100-80-5,3-Methyldihydrofuran-2,5-dione,as a common compound, the synthetic route is as follows.
5,6-dimethoxybenzo[d]thiazole (l.58g, 8.09mmol) was added to a sealed tube and back evacuated with N2 (2x). THF (40mL) was added, and the reaction mixture was cooled to -78C. rt-BuLi (1.5M in Hex, 5.6mL, 8.9mmol) was added, and the reaction mixture was stirred at -78C for 30 min. 3-methyldihydrofuran-2,5-dione (l.02g, 8.90mmol) was added, and the reaction mixture was allowed to warm to RT over a period of 4 hours. HC1 (1N) was added until the aqueous layer was pH ~ 4. The aqueous layer was then extracted with EtOAc (3x). The organic layers were combined, dried over MgS04, filtered, and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (eluting ACN/H20 with 0.05% TFA). The fractions containing all product isomers were combined, diluted with H20, and extracted with EtOAc (3x). The organics were combined, dried over MgS04, filtered, and concentrated under reduced pressure. The racemic mixture was resolved by Chiral-SFC (CHIRACEL OJ-H (250mmx2lmm), 25% MeOH in C02) to afford four peaks. Concentration of the third eluting peak afforded 4-(5,6-dimethoxy-l,3-benzothiazol-2-yl)-2-methyl-4- oxobutanoic acid. LCMS (CI4HI6N05S) (ES, m/z): 310 [M+H]+. 1H NMR (500MHz, MeOD- d4) d 7.65 (s, 1H), 7.59 (s, 1H), 3.96 (s, 3H), 3.97 (s, 3H), 3.69 (dd, =l8Hz, 8.8Hz, 1H), 3.28 (dd, =l8Hz, 5.5Hz, 1H), 3.15-3.08 (m, 1H), 1.33 (d, =7.3Hz, 3H).
4100-80-5, As the paragraph descriping shows that 4100-80-5 is playing an increasingly important role.
Reference£º
Patent; MERCK SHARP & DOHME CORP.; ALTMAN, Michael, D.; CASH, Brandon, D.; CUMMING, Jared, N.; DEMONG, Duane, E.; HAIDLE, Andrew, M.; JEWELL, James, P.; LARSEN, Matthew, A.; LU, Min; OTTE, Ryan, D.; TAOKA, Brandon, M.; TROTTER, Benjamin Wesley; TRUONG, Quang, T.; (97 pag.)WO2019/195063; (2019); A1;,
Tetrahydrofuran – Wikipedia
Tetrahydrofuran | (CH2)3CH2O – PubChem