Ammonia → HCID 26074839, compound

Sodium hydride (3.21 g, ca. 60% in oil, 80.6 mmol) was added to a 1,4-dioxane (100 mL) solution of 4-methoxyphenol (2.50 g, 20.1 mmol) at room temperature, and the mixture was stirred at room temperature for 10 minutes. (2S)-2-Chlorobutyric acid (2.95 g, 24.2 mmol) was added to the mixture at 100° C., and then the resulting mixture was heated at 100° C. for 30 minutes. After the reaction mixture was cooled to room temperature, water and 2 M hydrochloric acid were added to the reaction mixture. The resulting mixture was extracted three times with ethyl acetate, and the organic layer thus obtained was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and thus a mixture containing (2S)-2-(4-methoxyphenoxy)butyric acid was obtained. Carbonyldiimidazole (4.89 g, 30.2 mmol) was added to a tetrahydrofuran (100 mL) solution of the mixture described above, and the resulting mixture was stirred at room temperature for 30 minutes. Subsequently, a 28% aqueous ammonia solution (50 mL, excess amount) was added to the mixture at room temperature, and the resulting mixture was stirred for 20 minutes. Water was added to the reaction mixture, and the resulting mixture was extracted three times with ethyl acetate. The organic layer thus obtained was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-41:4, v/v) to give the title compound (3.66 g, yield: 87%).

1. temperaturethe resulting mixture was heated at 100° C. for 30 minutes
2. temperatureAfter the reaction mixture was cooled to room temperature
3. extractionThe resulting mixture was extracted three times with ethyl acetate
4. customthe organic layer thus obtained
5. washwas washed with water
6. dry with materialdried over anhydrous sodium sulfate
7. distillationThe solvent was distilled off under reduced pressure
8. additionthus a mixture containing (2S)-2-(4-methoxyphenoxy)butyric acid
9. customwas obtained
10. stirringthe resulting mixture was stirred at room temperature for 30 minutes
11. stirringthe resulting mixture was stirred for 20 minutes
12. extractionthe resulting mixture was extracted three times with ethyl acetate
13. customThe organic layer thus obtained
14. washwas washed with water
15. dry with materialdried over anhydrous sodium sulfate
16. distillationThe solvent was distilled off under reduced pressure
17. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-41:4, v/v)

ORD record

ord-a9d46cb8813544c287c461de14f3d753

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233958B2