Acetic Acid → 1,3-Diethyl 2-[[(4-methyl-3-thienyl)amino]methylene]propanedioate

To a solution of methyl 3-amino-4-methylthiophene-2-carboxylate (commercially available from Avocado, catalog number 10115, 5.00 g, 29.2 mmol) in 95% ethanol (25 mL) was added 1.0 N NaOH (35 mL). The mixture was heated to reflux and stirred for 2.5 hrs. The resulting solution was cooled to room temperature before the addition of glacial acetic acid (2.05 mL, 35.8 mmol). After stirring for 5 minutes at room temperature, diethyl ethoxymethylenemalonate (DEEM, 6.5 mL, 32.2 mmol) was added. The mixture was stirred vigorously until it nearly solidified (ca. 5 min), and then it was left standing at room temp for 3 hours. 95% ethanol (60 mL) was added, and the mixture was warmed on a steam bath until solution was achieved. Water (50 mL) was added with continued heating on the steam bath, resulting in a slightly cloudy solution. The flask was removed from the steam bath and allowed to cool to room temp and then placed in a 0° C. refrigerator, at which point crystallization of the product as fine white filaments was rapid. After standing at 0° C. for. 2 hours, the mixture was filtered. The collected solid was washed with 50% ethanol/water and dried, affording a white solid (5.79 g). The filtrate was diluted with water to a total volume of 500 mL, left overnight at 0° C., and filtered to afford a second crop (0.96 g) that was of equal purity to the first crop by HPLC analysis.

1. temperatureThe mixture was heated
2. temperatureto reflux
3. stirringAfter stirring for 5 minutes at room temperature
4. stirringThe mixture was stirred vigorously until it
5. custom(ca. 5 min)
6. waitit was left
7. waitstanding at room temp for 3 hours
8. temperaturethe mixture was warmed on a steam bath until solution
9. temperaturewith continued heating on the steam bath
10. customresulting in a slightly cloudy solution
11. customThe flask was removed from the steam bath
12. customplaced in a 0° C.
13. customat which point crystallization of the product as fine white filaments
14. customAfter standing at 0° C.
15. filtration2 hours, the mixture was filtered
16. washThe collected solid was washed with 50% ethanol/water
17. customdried

ORD 기록

ord-18cad0b4d8a44beb9089ffca030accd4

출처 데이터셋

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06852731B2