反应详情

温度

-78 °C

(R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(3-bromo-2,6-difluoro-benzyl) ester (3.9 g, 8 mM) was dissolved in tetrahydrofuran (120 mL), trisopropylborate (3.1 g, 17 mM) was added and the mixture was cooled to −78° C. At this low temperature n-butyllithium (7.8 mL, 1.6N) was added drop by drop with stirring. The mixture was stirred for 45 min at −78° C., for another 45 min at −50° C. and for 15 min at 0° C. Acetic acid (4.4 mL, 50%) was added slowly with stirring (0–5° C.), followed by hydrogen peroxide (1.3 mL, 35%). Stirring continued with cooling for another 45 min and for 1 h at room temperature. The mixture was partitioned between water and diethylether, organic phases were pooled, washed with water, sodium thiosulfate solution (5%), brine and dried with Na2SO4 to yield after evaporation a light yellow oil (4.1 g). This residue was purified by column chromatography (silica gel; n-hexane/ethylacetate 1:1) to yield 0.93 g (28%) of the product as a colorless oil. MS (ISP): 418.2 (M+NH4)+.

1. additiontrisopropylborate (3.1 g, 17 mM) was added
2. stirringThe mixture was stirred for 45 min at −78° C., for another 45 min at −50° C. and for 15 min at 0° C
3. stirringwith stirring (0–5° C.)
4. stirringStirring
5. temperaturewith cooling for another 45 min and for 1 h at room temperature
6. customThe mixture was partitioned between water and diethylether, organic phases
7. washwashed with water, sodium thiosulfate solution (5%), brine
8. dry with materialdried with Na2SO4
9. customto yield
10. customafter evaporation a light yellow oil (4.1 g)
11. customThis residue was purified by column chromatography (silica gel; n-hexane/ethylacetate 1:1)