Process for synthesizing a CETP inhibitor
View Patent ↗An efficient process is disclosed for producing the compound of formula I, which is the CETP inhibitor anacetrapib, which raises HDL-cholesterol and reduces LDL-cholesterol in human patients and may be effective for treating or reducing the risk of developing atherosclerosis:
1. A process for synthesizing the compound of Formula I:
comprising the step of combining the compounds of formula II and III
in the presence of a phase transfer catalyst and a base in a solvent, wherein the base is an alkali metal hydroxide, carbonate, hydrogen carbonate, phosphate, hydrogen phosphate, or dihydrogen phosphate.
2. The process of claim 1 , wherein the phase transfer catalyst is a tetraalkylammonium halide, a crown ether, or a quaternary phosphonium halide.
3. The process of claim 2 , wherein the solvent is dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), acetonitrile, N,N-dimethylacetamide (DMAC), 1,3-dimethyl-2- imidazolidinone (DMI), N-methyl-2-pyrrolidone (NMP), sulfolane, isopropyl acetate, tetrahydrofuran, or 2-methyltetrahydrofuran, or a combination thereof.
4. The process of claim 3 , wherein the base is K 2 CO 3 , Na 2 CO 3 , Cs 2 CO 3 , K 3 PO 4 , K 2 HPO 4 , KOH, or NaOH.
5. The process of claim 4 , wherein the catalyst is a tetraalkylammonium iodide.
6. The process of claim 5 , wherein the solvent is DMF, acetonitrile, or DMSO.
7. The process of claim 6 , wherein the catalyst is tetrabutylammonium iodide.
8. The process of claim 7 , wherein the temperature of the reaction is 50-100° C.
9. The process of claim 8 , wherein the solvent is DMF.
10. The process of claim 8 , wherein the solvent is acetonitrile.
11. The process of claim 8 , wherein the solvent is DMSO.