Malonic Acid → 3-Amino-3-(pyridin-3-yl)propanoic acid

Temperature

78 °C

Ammonium acetate (194.28 g, 2.52 mol) was suspended in ethanol (285 g). A solution of pyridine-3-carbaldehyde (62.9 g, 1.68 mol) in ethanol (80 g) was added to the suspension within 10 min at 15° C.-20° C. The reaction mixture was stirred for 1 h until a clear yellowish solution was formed. A suspension of malonic acid (174.86 g, 1.68 mol) in ethanol (235 g) was then added (within 30 min.) After stirring for 30 min at ambient temperature the reaction mixture was heated for 5 h to reflux (78° C.). Gas evolution was observed. After 3-4 h a white solid started to precipitate. The orange colored suspension was cooled to 15° C.-20° C., and a thick slurry was obtained. To this slurry was added methanol (80 g) and the reaction mixture was again heated to reflux (65° C.). The suspension was filtered hot, and the filtercake was washed with three portions of hot methanol (120 g) (at a temperature of 55° C.-65° C.). The wet product was dried in vacuo at 70° C.-80° C. to yield the product as a colorless solid (137.73 g, 49.3%). LC purity 95.8%

1. customwas formed
2. additionwas then added (within 30 min.)
3. stirringAfter stirring for 30 min at ambient temperature the reaction mixture
4. temperaturewas heated for 5 h
5. waitAfter 3-4 h a white solid started
6. customto precipitate
7. temperatureThe orange colored suspension was cooled to 15° C.-20° C.
8. customa thick slurry was obtained
9. temperaturethe reaction mixture was again heated
10. temperatureto reflux (65° C.)
11. filtrationThe suspension was filtered hot
12. washthe filtercake was washed with three portions of hot methanol (120 g) (at a temperature of 55° C.-65° C.)
13. customThe wet product was dried in vacuo at 70° C.-80° C.

ORD record

ord-9f10d55ac1954e2391fb555b238fb673

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06673926B2