1,1'-Carbonyldiimidazole → Ethyl 3-(5-chloro-2-methoxyphenyl)-3-oxopropanoate

温度

45 °C

A 3000 mL 3-necked round-bottomed flask flushed with nitrogen was charged with magnesium ethoxide (67.46 g, 589.51 mmoles) and THF (1100 mL), and the resulting mixture was stirred as ethyl hydrogen malonate (162.26 g, 1.18 moles; 145.00 mL diluted in 100 ml of THF) was added and the mixture was heated at 45° C. for 4 hours. Meanwhile, a 2000 mL 3-necked round-bottomed flask flushed with nitrogen was charged with 5-chloro-2-methoxybenzoic acid (100 g, 536 mmoles) and THF (600 mL). To this mixture stirring at room temperature was added 1,1′-carbonyldiimidazole (95.59 g, 589.5 mmoles) in portions to avoid excess foaming. After stirring for 3 hours at room temperature the second solution was added gradually to the first solution. After addition the reaction mixture was heated to 45° C. After 20 hours, the reaction mixture was concentrated under reduced pressure before adding ethyl acetate (1 L) followed by 2 N HCl (500 mL). After mixing, the layers were separated and the organic phase was washed sequentially with 2 N HCl (500 mL), saturated sodium bicarbonate (500 mL), and water (500 mL). The organic phase was concentrated under reduced pressure, the residue taken up in ethyl acetate (1000 mL) and concentrated again to afford the title compound (104.94 g).

1. customA 3000 mL 3-necked round-bottomed flask flushed with nitrogen
2. additionwas added
3. customMeanwhile, a 2000 mL 3-necked round-bottomed flask flushed with nitrogen
4. stirringAfter stirring for 3 hours at room temperature the second solution
5. additionwas added gradually to the first solution
6. additionAfter addition the reaction mixture
7. temperaturewas heated to 45° C
8. concentrationthe reaction mixture was concentrated under reduced pressure
9. additionbefore adding ethyl acetate (1 L)
10. additionAfter mixing
11. customthe layers were separated
12. washthe organic phase was washed sequentially with 2 N HCl (500 mL), saturated sodium bicarbonate (500 mL), and water (500 mL)
13. concentrationThe organic phase was concentrated under reduced pressure
14. concentrationconcentrated again

ORDレコード

ord-eb276bee625e48fc8e75d9806512d5d3

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08841314B2