Resolving and racemization method for 1-amino-1,2,3,4-tetrahydronaphthalene

Abstract

The invention provides a resolving and racemization method for 1-amino-1,2,3,4-tetrahydronaphthalene. The method comprises the following steps of: reducing 3,4-dihydro-1-(2H)-naphthalene ketoxime into DL-1-amino-1,2,3,4-tetrahydronaphthalene; and resolving DL-1-amino-1,2,3,4-tetrahydronaphthalene into optically pure (S)-1-amino-1,2,3,4-tetrahydronaphthalene and (R)-1-amino-1,2,3,4-tetrahydronaphthalene by using an acidic resolving agent, or oxidizing chiral secondary amine into corresponding imine or derivatives thereof, reducing into DL-secondary amine and continuously resolving to obtain a single optical product. The enantiomeric excess (ee) value of the obtained product is more than 99.5 percent; and the yield of one-time resolving exceeds 30 percent, and the total yield of the route reaches 46 to 54 percent. Compared with the methods reported by various documents and patents at present, the method has obvious technological and economical advantages.

Description

technical field [0001] The invention relates to a resolution and racemization method of a class of chiral secondary amines, in particular to a resolution and racemization method of 1-amino-1,2,3,4-tetralin. Background technique [0002] Chiral drugs are a hot spot in the research and development of new drugs in recent years. In the past 20 years, more than half of the new drugs launched in the world are chiral. Chemically pure mixed 1-amino-1,2,3,4-tetralin, optically pure (S)-1-amino-1,2,3,4-tetralin and (R)-1 -Amino-1,2,3,4-tetralin is an important pharmaceutical intermediate and an intermediate commonly used in the research and development of small molecule innovative drugs. E.g: [0003] Document [Bioorganic & Medicinal Chemistry 12 (2004), 4189-4196] report, the 1-amino-1 of mixed rotation, 2,3, the compound of 4-tetralin is used for synthesizing following formula I structure, and this class compound has very good Appetite-reducing and weight-loss effects. [0004]...

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Problems solved by technology

[0011] Although the design idea of ​​the above synthetic route is very good, its actual effect is very general. When reducing chiral imines, a low temperature of -30°C is required, and because the selectivity of chiral reduction is not very good, it is necessary to use Chiral L-tartaric acid salt purification, that is, still need to use L-tartaric acid for resolution, the overall yield is relatively low, only 18%

[0012] In addition, about the racemization of (S)-1-amino-1,2,3,4-tetralin or (R)-1-amino-1,2,3,4-tetralin, there are few reports in the literature. less, and there are deficiencies (the problem of benzylamine being hydrogenated by using palladium catalyzed dehydrogenation as imine; the use of nickel and cobalt catalyzed dehydrogenation as imine has a large amount of catalyst, catalyst deactivation, and long reaction time question)

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