Ammonia → HCID 117701113, compound

Carbonyldiimidazole (1.07 g, 6.60 mmol) was added to a tetrahydrofuran (15 mL) solution of the compound obtained in Reference Example 81 (1.03 g, 4.40 mmol) at room temperature, and the mixture was stirred at the same temperature for 40 minutes. A 28% aqueous ammonia solution (7 mL, excess amount) was added to the mixture at room temperature, and the resulting mixture was stirred at the same temperature for 20 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). Subsequently, trifluoroacetic anhydride (0.612 mL, 4.40 mmol) was added to a methylene chloride (20 mL) solution of the compound thus obtained and pyridine (0.708 mL, 8.79 mmol) at 0° C., and the mixture was stirred at the same temperature for 20 minutes. Water and a saturated aqueous solution of ammonium chloride were added to the reaction mixture at 0° C., and the mixture was extracted three times with methylene chloride. The organic layer thus obtained was washed with water and a 1 M aqueous sodium hydroxide solution sequentially, 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=9:1→2:1, v/v) to give the title compound (867 mg, yield: 92%).

1. stirringthe resulting mixture was stirred at the same temperature for 20 minutes
2. extractionthe resulting mixture was extracted three times with ethyl acetate
3. dry with materialdried over anhydrous sodium sulfate
4. distillationThe solvent was distilled off under reduced pressure
5. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→ethyl acetate, v/v)
6. customthus obtained
7. extractionthe mixture was extracted three times with methylene chloride
8. customThe organic layer thus obtained
9. washwas washed with water
10. dry with materiala 1 M aqueous sodium hydroxide solution sequentially, and then dried over anhydrous sodium sulfate
11. distillationThe solvent was distilled off under reduced pressure
12. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1→2:1, v/v)

ORD record

ord-26f6ae239bdb491dbf98d3f5326828bf

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233958B2