Hydrochloric Acid → 3-Hydroxy-thiophene-2-carboxylic acid methyl ester

To dry methanol (81 mL), under nitrogen, was added sodium metal (3.68 g, 304 mmol). After H2 evolution ceased, the solution was cooled to 0° C. and methyl thioglycolate (10 g, 179 mmol) was added dropwise. A solution of methyl-2-chloroacrylate (10.88 g, 179 mmol) in methanol (21 mL) was then added slowly, resulting in the formation of yellow precipitate. The solution was allowed to warm to ambient temperature and stirred for 2 h. The solvent was removed in vacuo to give a dark yellow solid that was acidified to pH 2 with 4 N HCl. The resulting aqueous solution was extracted with dichloromethane (3×150 mL) and the combined organic solutions were washed with water (3×150 mL), dried over MgSO4, filtered, and concentrated to give a dark oil. The oil was subjected to column chromatography on silica gel (20:1 hexanes/ethyl acetate) to give (12) (18.4 g) as a crystalline solid in 64% yield. TLC (20:1 hexanes/ethyl acetate) Rf 0.47; 1H NMR (CDCl3) δ 9.58 (s, 1H), 7.59 (d, J=5.7 Hz, 1H), 6.75 (d, J=4.8 Hz, 1H), 3.90 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 166.8, 164.7, 131.7, 119.4, 52.2; EI-MS m/e 158.0039 (M+ calculated 158.0038 for C6H6O3S).

1. customresulting in the formation of yellow precipitate
2. temperatureto warm to ambient temperature
3. customThe solvent was removed in vacuo
4. customto give a dark yellow solid
5. extractionThe resulting aqueous solution was extracted with dichloromethane (3×150 mL)
6. washthe combined organic solutions were washed with water (3×150 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a dark oil

ORDレコード

ord-a4768f02ac524a229a2f0d9867f7e399

出典データセット

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07452730B2