Methyl Thioglycolate → Methyl 3-amino-5-chloro-2-thiophenecarboxylate

In a flame dried flask under a nitrogen atmosphere, and with mechanical stirring, a solution of about 1.2 g (0.05 mole) of sodium metal dissolved in 30 ml of dry methanol was treated dropwise with 2.35 g (1.98 ml, 0.022 mole) of methyl thioglycolate while maintaining the temperature below 25° C. A solution of 2.70 g (0.022 mole) of 3,3-dichloroacrylonitrile [R. L. Soulen, D. B. Clifford, F. F. Crim and J. A. Johnston, J. Org. Chem. 36 (22), 3386-3391 (1971)] and 10 ml of methanol was then added dropwise at a rate such as to keep the reaction temperature <28° C. The reaction mixture became cloudy and orange. Stirring was continued for an hour. The mixture was concentrated under reduced pressure, was diluted with water, and was extracted five times with 60 ml portions of chloroform. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure to furnish an oil which was chromatographed under moderate pressure ("flash" chromatography) on a column of silica gel (Woelm 32-63 micrometers, i.d. 5 cm×height 18 cm); the eluant was isopropyl ether; 15 ml fractions were taken. Fractions 15-20 were combined and evaporated to give methyl 3-amino-5-chloro-2-thiophenecarboxylate as a colorless solid: m.p. 99°-101° C.; yield 0.60 g (14%); ir (KBr) 3448 cm-1, 3343, 1674, 1615, 1546, 1455, 1425 among others; 1H-nmr (CDCl3) delta 3.8 ppm (s, 3H), 5.3 (broad s, 2H), 6.4 (s, 1H); mass spectrum 191 (molecular ion), 159 (-32, CH3OH, parent peak) and others.

1. customIn a flame dried flask under a nitrogen atmosphere
2. temperaturewhile maintaining the temperature below 25° C
3. customthe reaction temperature <28° C
4. waitwas continued for an hour
5. concentrationThe mixture was concentrated under reduced pressure
6. additionwas diluted with water
7. extractionwas extracted five times with 60 ml portions of chloroform
8. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
9. filtrationfiltered
10. customevaporated under reduced pressure
11. customto furnish an oil which
12. customwas chromatographed under moderate pressure ("flash" chromatography) on a column of silica gel (Woelm 32-63 micrometers, i.d. 5 cm×height 18 cm)
13. customevaporated

ORD 기록

ord-b980b5470f774c959a870770b9af1883

출처 데이터셋

uspto-grants-1989_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US04797486