Toluene → HCID 59750703, compound

Temperature

0 °C

Under a nitrogen atmosphere and at 0° C., triethylamine (81.5 μl, 0.586 mmol) and diphenylphosphoric azide (126 μl, 0.586 mmol) were added to a toluene solution (5 ml) of the 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)butyric acid (200 mg, 0.533 mmol) obtained in Example 200, followed by stirring at 0° C. for 2 hours. The reaction mixture was heated under reflux for 3 hours. After cooling to room temperature and addition of ethanol (2 ml), the mixture was heated under reflux for further 2 hours. The reaction mixture was then concentrated. The residue thus obtained was dissolved in dichloromethane. The resulting solution was washed successively with a saturated aqueous solution of potassium bicarbonate, water and brine, dried over magnesium sulfate and then, concentrated. The residue thus obtained was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=1:3 eluate was concentrated. The solid thus obtained was recrystallized from ethyl acetate-hexane, whereby the title compound (129 mg, 0.309 mmol, 58%) was obtained as a white solid.

1. temperatureThe reaction mixture was heated
2. temperatureunder reflux for 3 hours
3. temperatureAfter cooling to room temperature
4. temperaturethe mixture was heated
5. temperatureunder reflux for further 2 hours
6. concentrationThe reaction mixture was then concentrated
7. customThe residue thus obtained
8. washThe resulting solution was washed successively with a saturated aqueous solution of potassium bicarbonate, water and brine
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated
11. customThe residue thus obtained
12. concentrationethyl acetate=1:3 eluate was concentrated
13. customThe solid thus obtained

ORD record

ord-ca61ff4e12184a919c43d6c7420a6afb

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07399775B2