反应详情

温度

-10 °C

A cooled (−10° C.) solution of commercially available 2-iodo-1,3-dimethoxybenzene (2.000 g; 7.57 mmol) in anh. THF (30 ml) was treated dropwise with a solution of 2 M isopropylmagnesium chloride in THF (5.10 ml; 10.20 mmol), and the mixture was further stirred at −10° C., under nitrogen, for 15 min. This mixture was then added dropwise to a cooled (−40° C.) solution of commercially available 4-methyldihydro-2H-pyran-2,6(3H)-dione (970 mg; 7.57 mmol) and CuI (360 mg; 1.89 mmol) in anh. THF (20 ml). Stirring was continued at −40° C. for 20 min., and 2 M aq. HCl (11.5 ml) was then added dropwise. Et2O (100 ml), and aq. sat. NH4Cl (30 ml) were added, and the separated organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Anh. DMF (20 ml), and Cs2CO3 (3.165 g; 9.71 mmol) were successively added, and stirring at rt was continued for 15 min. After cooling to 0° C., iodomethane (1.655 g; 11.66 mmol) was added dropwise, and the resulting mixture was further stirred at 0° C. for 10 min., and then at rt for 1.5 h. AcOEt (100 ml) and water (100 ml) were added, and the separated organic layer was further washed with brine (25 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=20/1) afforded methyl 5-(2,6-dimethoxyphenyl)-3-methyl-5-oxopentanoate as a yellow oil. LC-MS (conditions D): tR=0.97 min.; [M+H]+: 281.29 g/mol.

1. additionThis mixture was then added dropwise to
2. stirringStirring
3. waitwas continued at −40° C. for 20 min.
4. dry with materialthe separated organic layer was dried over anh. MgSO4
5. filtrationfiltered
6. concentrationconcentrated to dryness under reduced pressure
7. stirringstirring at rt
8. waitwas continued for 15 min
9. temperatureAfter cooling to 0° C.
10. stirringthe resulting mixture was further stirred at 0° C. for 10 min.
11. waitat rt for 1.5 h
12. washthe separated organic layer was further washed with brine (25 ml)
13. dry with materialdried over anh. MgSO4
14. filtrationfiltered
15. concentrationconcentrated to dryness under reduced pressure
16. customPurification by FC (DCM/MeOH=20/1)