(r)-alpha, Alpha-diphenyl -2 - Pyrrolidine Methanol Synthesis

CBS catalyst is one kind of the important chiral catalysts in asymmetric reductions of prochiral ketones, which have extremely high yield and optical yield. In this paper, (R)-α, α-diphenyl-2-pyrrolidinemethanol, which is a typical chiral ligand of CBS catalyst, was synthesized using Grignard reaction as main process, and three different ways to protect the functional groups of (R)-proline.In this paper, three routines to prepare (R)-α, α-diphenyl-2-pyrrolidine- methanol were compared and appraised, namely, the way using triphosgene as protect reagent, the way deriving to Proline-N-benzyl methyl ester and the way deriving to Proline-N-ethyl carbamate methyl ester. It was confirmed that, the third routine has a little less yield, but utilizes inexpensive raw materials, convenient operations and simple post treatment. Though triphosgene has toxicity, it is also inexpensive. All these merits make the third routine the best to apply in industrial process.Based on some related literatures, a further research was carried out on the reaction process which using triphosgene as protect reagent. It was suggested that: the dissolva-bility of (R)-proline in tetrahydrofuran improves as the solvent acidity improves. And this phenomenon can impact on the next step severely. This paper realised the routine using triphosgene as protect reagent, which has a narrrow-band optimum condition and sometime cannot be repeated, is not suit for industrial process.