反应详情

温度

-78 °C

A solution of 7.9 g of 4-bromo-1-methoxy-2-(3-methoxypropoxy)-benzene in 125 mL of tetrahydrofuran is cooled to −78° C. A solution of n-butyllithium (14.219 g of a 1.6 M solution in hexane) is added within 50 minutes. The reaction mixture is stirred for 90 minutes at −78° C. and treated slowly with 75 mL of a tetrahydrofuran solution of 8.93 g of (3S,5S)-5-tert-butoxycarbonyloxymethyl-3-isopropyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester. The resulting reaction mixture is stirred for 3 hours at −78° C. Finally the temperature is raised to −40° C. and the mixture stirred for 45 minutes. Acetic acid (4 mL) was added and the solvent removed by evaporation. The residue is dissolved in 100 mL of ethyl acetate and washed with two 75 mL portions of saturated sodium bicarbonate solution followed by one portion of 150 mL of water. The organic phase was dried and the solvent removed to give an oil. Chromatography on silica-gel, eluting with hexane/ethyl acetate gives, after combination of the product containing fractions and removal of the solvent, affords the title compound as an oil.

1. customThe resulting reaction mixture
2. stirringis stirred for 3 hours at −78° C
3. temperatureFinally the temperature is raised to −40° C.
4. stirringthe mixture stirred for 45 minutes
5. customthe solvent removed by evaporation
6. dissolutionThe residue is dissolved in 100 mL of ethyl acetate
7. washwashed with two 75 mL portions of saturated sodium bicarbonate solution
8. customThe organic phase was dried
9. customthe solvent removed
10. customto give an oil
11. washChromatography on silica-gel, eluting with hexane/ethyl acetate
12. customgives
13. additionafter combination of the product containing
14. customfractions and removal of the solvent