Synthesized compounds 1, 2 and 8. These reactions were successfully reproduced at large scales (up to 10 times).
- Synthesis of compound 1: Maintaining the reaction temperature at -78 oC is critical for achiving disubstitution. The crude materials were purifed by crystallization in hexanes at -35 oC instead of using column chromatography for large scale reaction.
- Synthesis of compound 2: The crude materials were purified by crystallization in ethanol for large scale reaction.
- Synthesis of compound 8: Ether as a solvent worked better than THF in this reaction. Increasing n-BuLi from 2.1 eq to 2.2-2.3 eq and 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane from 2.3 eq to 2.4-2.5 eq resulted in better reaction yields. Longer time (1-3 hs) at 0 oC for the lithiation reaction was needed for large scale reaction. The crude materials were purfied by crystallization in ethanol.
The recation yields (determined by H NMR spectra of the crude materials) are higher than 90-95%.