With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.768-66-1,2,2,6,6-Tetramethylpiperidine,as a common compound, the synthetic route is as follows.
Starting from commercially available pyrrole-2-carbaldehyde 1, synthesis of L- Ala- [5- (HOCH2)-2-boroPro] (I) was achieved via nine steps in an overall yield of 17%. First, pyrrole-2-carbaldehyde 1 was deprotonated with sodium hydride in tetrahydrofuran and then reacted with di-tert-butyl dicarbonate to give N-Boc-pyrrole-2-carbaldehyde 2 (see Tietze, et al. Synthesis of N-protected 2-hydroxymethylpyrroles and transformation into acyclic oligomers. Synthesis (1996), 7: 851-857). Reduction of the carbaldehyde 2 with lithium borohydride at-10C yielded the hydroxymethyl compound 3. The hydroxylmethyl group of compound 3 was then protected with a tetrahydropyranyl group to form the THP ether 4. Total yield of the first three steps was 78%, with purification by silica gel flash chromatography at each step. The protected pyrrole was deprotonated with LiTMP (generated from n-butyl lithium and tetramethylpiperidine in THF at-78C) (see Kelly, et al. The efficient synthesis and simple resolution of a prolineboronate ester suitable for enzyme-inhibition studies. Tetrahedron (1993), 49 (5): 1009-16) and quenched with trimethyl borate, then HC1 was added to hydrolyze the dimethyl boronate to give the boronic acid 5. Without further purification, compound 5 was hydrogenated over 5% Pt/C in ethyl acetate to afford pyrrolidine-2-boronic acid 6. Crude 6 was stirred with 1. 05eq. (+) -pinanediol in ether at room temperature and then purified by silica gel flash chromatography to yield the protected 5-hydroxymethylboroPro pinanediol ester 7 in 60% yield over these three steps. Removal of the tert-butoxycarbonyl (Boc) group with 4 N HC1 in dioxane gave intermediate compound 8 in a yield of 94%. Compound 8 was coupled with N-Boc-L-Ala-OH in the presence of HATU and DIPEA, then the Boc and pinane protecting groups were deprotected with BC13 to give the target dipeptide boronate I in a 38% yield over the last two steps., 768-66-1
As the paragraph descriping shows that 768-66-1 is playing an increasingly important role.
Reference：
Patent; TRUSTEES OF TUFTS COLLEGE; WO2005/82348; (2005); A2;,
Piperidine – Wikipedia
Piperidine | C5H11N – PubChem