Ammonia → HCID 117701134, compound

Tripotassium phosphate (8.17 g, 38.5 mmol) and ethyl 2-bromobutyrate (4.77 mL, 32.6 mmol) were added to an acetone (24 mL) solution of cyclopropyl(4-hydroxyphenyl)methanone (4.80 g, 29.6 mmol) at room temperature, and the mixture was stirred for 4 hours under reflux. Tripotassium phosphate (1.57 g, 7.40 mmol) and ethyl 2-bromobutyrate (1.08 mL, 7.40 mmol) were added to the mixture at room temperature, and the resulting mixture was stirred for 3 hours under reflux. After the reaction mixture was cooled to room temperature, water was added to the reaction mixture, and the resulting mixture was extracted once with acetone. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1→1:1, v/v). Subsequently, the compound thus obtained was dissolved in water (45 mL), then 5 M aqueous sodium hydroxide solution (8.78 mL, 44.4 mmol) was added to the mixture at room temperature, and the resulting mixture was stirred at the same temperature for 2 hours. Water and a saturated aqueous solution of ammonium chloride were added to the reaction mixture, and the mixture was extracted three times with ethyl acetate, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. Carbonyldiimidazole (7.20 g, 44.4 mmol) was added to a tetrahydrofuran (150 mL) solution of the compound thus obtained (7.35 g, 29.5 mmol) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. A 28% aqueous ammonia solution (30 mL, excess amount) was added to the mixture at room temperature, and the resulting mixture was stirred at the same temperature for 30 minutes. Water was added to the reaction mixture, and the resulting mixture was extracted three times with ethyl acetate, 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=1:1→ethyl acetate, v/v) to give the title compound (6.41 g, yield: 87%).

1. temperatureunder reflux
2. stirringthe resulting mixture was stirred for 3 hours
3. temperatureunder reflux
4. extractionthe resulting mixture was extracted once with acetone
5. distillationThe solvent was distilled off under reduced pressure
6. customthe resulting residue was purified by silica gel column chromatography (hexane
7. customSubsequently, the compound thus obtained
8. stirringthe resulting mixture was stirred at the same temperature for 2 hours
9. extractionthe mixture was extracted three times with ethyl acetate
10. dry with materialdried over anhydrous sodium sulfate
11. distillationThe solvent was distilled off under reduced pressure
12. customthus obtained (7.35 g, 29.5 mmol) at room temperature
13. stirringthe mixture was stirred at the same temperature for 30 minutes
14. stirringthe resulting mixture was stirred at the same temperature for 30 minutes
15. extractionthe resulting mixture was extracted three times with ethyl acetate
16. dry with materialdried over anhydrous sodium sulfate
17. distillationThe solvent was distilled off under reduced pressure
18. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→ethyl acetate, v/v)

ORD record

ord-d5d7e659e3634c93ba831a7ca89aebbf

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233958B2