Method for resolving 3-amino-3-phenylpropanol

Abstract

The invention relates to a method for resolving 3-amino-3-phenylpropanol. Tolylsulfonyl proline is used as a resolving agent to effectively resolve S-3-amino-3-phenylpropanol and R-3-amino-3-phenylpropanol. Compared with the prior art, the invention has the advantage of reasonable technique, and is simple to operate; the resolving agent is prepared from cheap and accessible proline; the obtained product has high optical purity and chemical purity; and thus, the invention is suitable for industrialized large-scale production of chiral 3-amino-3-phenylpropanol.

Description

technical field [0001] The invention relates to the production of a chiral 3-amino-3-phenylpropanol, in particular to a method for resolving 3-amino-3-phenylpropanol. Background technique [0002] Chiral 3-amino-3-phenylpropanol is an important pharmaceutical intermediate, especially S-3-amino-3-phenylpropanol (1) is a key intermediate of various chiral drugs and can be used for Synthesis of Dapoxetine (2), anti-AIDS drug Selzentry (Maraviroc) (3). Dapoxetine is the first oral drug (tablet) of this type approved for the treatment of premature ejaculation in the world. Johnson & Johnson is currently approved for marketing in Finland, Sweden, Portugal, Austria, Italy, Spain and other countries in Europe. The synthesis method of Dapoxetine is as follows: [0003] [0004] The key of synthesis is to solve chiral intermediate S-3-amino-3-phenylpropanol, and the main synthetic method of S-3-amino-3-phenylpropanol has at present; 1) through S-3-amino-3 - Obtained by reduction ...

AI Technical Summary

Problems solved by technology

[0004] The key of synthesis is to solve chiral intermediate S-3-amino-3-phenylpropanol, and the main synthetic method of S-3-amino-3-phenylpropanol has at present; 1) through S-3-amino-3 -Obtained by reduction of phenylpropionic acid, while S-3-amino-3-phenylpropionic acid requires enzymatic resolution or asymmetric catalyzed synthesis, the raw materials are expensive and the cost is high

2) Catalyzed by some special enzymes, such as Nitin W. Fadnavis et al. using immobilized penicillin G acylase resolution (Tetrahedron: Asymmetry 17, 2006, 240-244), Oliver Torre et al. using Lipase resolution (Tetrahedron: Asymmetry 17, 2006, 860-866) These methods are either relatively rare enzymes and expensive, or the EE value of the splitting effect is not high, and it is difficult to industrialize production

3) Synthesis by chiral asymmetry, such as Shafi A. et al. starting from methyl cinnamate through the asymmetric oxidation of (DHQ)2PHAL, OsO4, to synthesize, (Tetrahedron: Asymmetry 18, 2007, 2099-2103), Pinak M.Chincholkar et al. started to synthesize chiral 3-hydroxy azetidin-2-one compounds from L-diethyl tartrate, and then reduced ring-opening to obtain S-3-amino-3-phenylpropanol, (Tetrahedron 65, 2009, 2605-2609) synthesis steps must be more than 7-8 steps, it is difficult to scale up production

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