Water → 2-(2,6-Dichlorobenzamido)pent-4-enoic acid methyl ester

Allylglycine (10.11 g) was dissolved in a mixed solvent of 2N aqueous sodium hydroxide solution (176 ml) and dioxane (175 ml), and 2,6-dichlorobenzoyl chloride (15.10 ml) was added dropwise thereto, followed by stirring the resulting mixture at room temperature for 10 hours. After concentrating the reaction solution to remove dioxane, water (150 ml) was added thereto and the resulting solution was washed with ether. Aqueous layer was acidified by adding 3N hydrochloric acid in small portions thereto, and extracted 3 times with ethyl acetate. Organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was recrystallized from hexane/ethyl acetate mixed solvent to obtain 2-(2,6-dichlorobenzamido)pent-4-enoic acid (23.48 g). (2) Under an argon atmosphere, a solution of 2-(2,6-dichlorobenzamido)pent-4-enoic acid (23.48 g) in methanol (250 ml) was cooled to 0° C. Thionyl chloride (10.70 ml) was added dropwise to the solution while keeping the reaction temperature not higher than 110° C., and thereafter the resulting mixture was stirred at room temperature for 5.5 hours. Water was added to the reaction solution, and sodium hydrogen carbonate was added thereto in small portions to neutralize it. After concentrating the reaction solution to remove methanol, aqueous layer was extracted twice with ethyl acetate. Organic layers were washed 3 times with water and once with saturated brine, and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was recrystallized from hexane/ethyl acetate mixed solvent to obtain 2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (21.70 g). NMR (H1, CDCl3): δ 2.55-2.61 (1H, m), 2.68-2.75 (1H, m), 3.72 (3H, s), 4.88 (1H, td, J=7.8, 5.4 Hz), 5.06-5.13 (2H, m), 5.64-5.74 (1H, m), 6.33 (1H, brd, J=7.1 Hz), 7.17-7.26 (3H, m)

1. customhigher than 110° C.
2. additionwas added
3. concentrationAfter concentrating the reaction solution
4. customto remove methanol, aqueous layer
5. extractionwas extracted twice with ethyl acetate
6. washOrganic layers were washed 3 times with water
7. dry with materialonce with saturated brine, and dried over anhydrous sodium sulfate
8. customAfter removing anhydrous sodium sulfate
9. filtrationby filtration
10. concentrationthe filtrate was concentrated
11. customThe residue was recrystallized from hexane/ethyl acetate mixed solvent

ORD record

ord-873f1a34fbf140cab6f9f6d145750021

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07566724B2