反应详情

A sol. of 2-(2,6-dichloro-4-methyl-phenoxy)-ethanol (18.6 g, 84 mmol) in THF (360 mL) was cooled to 0° C. NaH (about 55% in oil, 6.60 g, about 153 mmol) was added in portions, and the mixture was stirred at rt for 30 min. A sol. of 2,5-dibrompyridine (18.0 g, 76.3 mmol) in THF (60 mL) was added dropwise, and the mixture was heated to reflux for 90 min. The mixture was allowed to cool to rt, and ice was added carefully. The solvents were partially removed under reduced pressure, and the residue was diluted with EtOAc. This mixture was washed with aq. sat. NH4Cl. The aq. layer was extracted back with EtOAc (2×). The combined org. extracts were washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 3:97) yielded the title compound (22.7 g, 79%). LC-MS: tR=1.13 min; ES+: 378.08.

1. temperaturethe mixture was heated
2. temperatureto reflux for 90 min
3. temperatureto cool to rt
4. additionice was added carefully
5. customThe solvents were partially removed under reduced pressure
6. additionthe residue was diluted with EtOAc
7. washThis mixture was washed with aq. sat. NH4Cl
8. extractionThe aq. layer was extracted back with EtOAc (2×)
9. washextracts were washed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customthe solvents were removed under reduced pressure
13. customPurification of the crude by FC (EtOAc/heptane 3:97)