Sodium Hydroxide → 2-Butyl-5-chloro-1H-imidazole-4-carbaldehyde

Temperatur

100 °C

31.72 g (250 mmol) of glycine methyl ester hydrochloride was added in a single portion to a solution of 10.13 g (250 mmol) of sodium hydroxide in 80 ml of methanol at 0° C. The temperature dropped to -10° C. The mixture was stirred for 10 minutes, during which time the temperature rose again to 0° C. 108.25 g (a 26.6 percent strength solution in toluene, 250 mmol) of methyl pentanimidate was added, and the mixture was stirred at room temperature for 3 hours. 35.64 g (about 92 percent strength, 275 mmol) of dimethylformamide dimethyl acetal then was added, during the course of 5 minutes. The reaction mixture was stirred for an additional 3 hours. 200 ml of toluene was added, and methanol and water were removed from the mixture by distillation in vacuo. Of the remaining 203.5 g, 91.68 g (corresponding to 112 mmol of methyl pentanimidate) was initially introduced at room temperature and treated with 65.09 g (416 mmol) of POCl3. The mixture was heated 15 100° C. for 1.5 hours and then 118.5 g of POCl3 /toluene was distilled off and the residue was treated with 121 ml of ethyl acetate and 408 ml of water. The pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution, and the phases were separated. The aqueous phase was extracted twice, each time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water, dried (MgSO4), and filtered and concentrated. The residue was dried in a high vacuum. 14.07 g of 2-butyl-5-chloroimidazole-4-carbaldehyde (HPLC content 79.9 percent) was obtained. This corresponds to a yield of 56 percent, based on the methyl pentanimidate.

1. additionThe temperature dropped to -10° C
2. customrose again to 0° C
3. stirringthe mixture was stirred at room temperature for 3 hours
4. stirringThe reaction mixture was stirred for an additional 3 hours
5. custommethanol and water were removed from the mixture by distillation in vacuo
6. distillation118.5 g of POCl3 /toluene was distilled off
7. additionthe residue was treated with 121 ml of ethyl acetate and 408 ml of water
8. additionThe pH was adjusted to 1, by addition of 18 ml of 30 percent strength sodium hydroxide solution
9. customthe phases were separated
10. extractionThe aqueous phase was extracted twice
11. washeach time with 200 ml of ethyl acetate, and the combined organic phases were washed with 200 ml of water
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated
15. customThe residue was dried in a high vacuum

ORD-Eintrag

ord-fc3f42f3c68e433a8b6a0848c211608a

Quelldatensatz

uspto-grants-1996_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05486617