Method for preparing optical pure 1-(1-naphthyl)ethylamine by separation

An ethylamine and optical technology, which is applied in the field of preparing optically pure 1-ethylamine, can solve the problems of high cost and difficulty in large-scale production, and achieve good results, high-efficiency preparation methods, and simple separation methods

An ethylamine and optical technology, which is applied in the field of preparing optically pure 1-ethylamine, can solve the problems of high cost and difficulty in large-scale production, and achieve good results, high-efficiency preparation methods, and simple separation methods

CN101407465AActive Publication Date: 2009-04-15WUXI APPTEC (TIANJIN) CO LTD +1
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  • Method for preparing optical pure 1-(1-naphthyl)ethylamine by separation
  • Method for preparing optical pure 1-(1-naphthyl)ethylamine by separation
  • Method for preparing optical pure 1-(1-naphthyl)ethylamine by separation

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] 1, the preparation of (S)-1-(1-naphthalene) ethylamine

[0013] Method A:

[0014] 1-(1-naphthalene) ethylamine (5g, 2.9mmol) and L-aspartic acid (3.9g, 2.9mmol) join in the mixed solution of dioxane (10ml) and water (100ml), heat to The reaction solution was clarified, cooled overnight, and filtered to obtain the aspartic acid salt of (S)-1-(1-naphthalene)ethylamine. Recrystallized with dioxane (1ml) and water (10ml), the obtained solid was added to water (50ml), and washed with K 2 CO 3 Adjust the pH to 9-10, extract three times with dichloromethane (60ml, 30ml, 20ml), combine the dichloromethane layers, wash with water (30ml), saturated brine (30ml) once each, and wash with anhydrous Na 2 SO 4 Dry, filter, and concentrate the filtrate to dryness to obtain light yellow oil (0.6g, yield: 24%)

[0015] Method B:

[0016] 1-(1-naphthalene) ethylamine (5g, 2.9mmol) and L-aspartic acid (3.9g, 2.9mmol) join in the mixed solution of dioxane (100ml) and water (10m...

Embodiment 2

[0022] 1, the preparation of (R)-1-(1-naphthalene) ethylamine

[0023] 1-(1-naphthalene) ethylamine (500g, 2.9mol) and D-aspartic acid (389g, 2.9mol) are added in the mixed solution of dioxane (1000ml) and water (1500ml), heated to reaction The liquid was clarified, cooled overnight, and filtered to obtain (R)-1-(1-naphthyl)ethylamine aspartic acid salt. Use dioxane (500ml) and water (750ml) to recrystallize, and the solid obtained joins in the water (500ml), with K 2 CO 3 Adjust the pH to 9-10, extract three times with dichloromethane (600ml, 300ml, 200ml), combine the dichloromethane layers, wash with water (300ml), saturated brine (300ml) once each, and wash with anhydrous Na 2 SO4 was dried, filtered, and the filtrate was concentrated to dryness to obtain a pale yellow oil (100 g, yield: 40%).

Embodiment 3

[0025] L, D- aspartic acid cross split

[0026] The mother liquor that obtains among the embodiment 1 or 2 is used K 2 CO 3 After alkalization, extract three times with dichloromethane (1000ml, 500ml, 300ml), wash with water (500ml), saturated brine (500ml) once each, and wash with anhydrous Na 2 Dry over SO4, filter, and concentrate the filtrate to dryness to give a pale yellow oil. Then add a mixed solution of dioxane (1000ml) and water (1500ml), D-aspartic acid or L-aspartic acid (276g) is added, heated to the reaction solution clarification, cooled overnight, filtered to obtain ( R)-1-(1-naphthalene)ethylamine aspartic acid salt or (S)-1-(1-naphthalene)ethylamine aspartic acid salt. Use dioxane (500ml) and water (750ml) to recrystallize, and the solid obtained joins in the water (1000ml), with K 2 CO 3 Adjust the pH to 9-10, extract three times with dichloromethane (1000ml, 500ml, 300ml), combine the dichloromethane layers, wash with water (500ml), saturated brine...

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Abstract

The invention relates to a method for preparing 1-(1-naphtaline) ethylamine possessing optical activity, which mainly solves problems of current process of expensive original raw material, long synthesizing process, low yield coefficient, and over-high cost and the like; the invention has chiral aspartic acid as chiral resolving agent, water or solution of water and dioxane as solvent; under a heating condition, racemate 1-(1-naphtaline) ethylamine is reacted with chiral aspartic acid to form enantiomeric salt. Then, according to different solubility of 1-(1-naphtaline) ethylamine to enantiomeric salt, splitting is carried out, and two configurations (S configuration and R configuration) of 1-(1-naphtaline) ethylamine are separated and prepared; chiral e.e. value for one time of splittingcan reach over 98 percent, with yield coefficient over 30 percent. The method is mainly used for preparing S configuration 1-(1-naphtaline) ethylamine and R configuration 1-(1-naphtaline) ethylamine drug intermediate possessing optical activity and template compound researched and developed by innovative small molecule drugs.

Description

Technical field: [0001] The invention relates to a method for preparing optically pure 1-(1-naphthalene)ethylamine, in particular to a method for obtaining optically pure (S)-1-(1-naphthalene) by splitting racemic 1-(1-naphthalene)ethylamine ) ethylamine and (R)-1-(1-naphthalene) ethylamine. Background technique: [0002] Chiral (S)-1-(1-naphthalene)ethylamine and (R)-1-(1-naphthalene)ethylamine are useful drug intermediates. Its preparation method generally has following several kinds: enzymatic resolution (Indian J.Chem.Sect.B 2005,44,1312-1316; J.Org.Chem.1997,62,3488-3495); Chemical resolution: by hand α-Hydroxynaphthylacetic acid (US6342636; Tetrahedron: asymmetry, 1998, 9, 2219-2212) or protected chiral glycerol derivatives resolution (Tetrahedron: asymmetry, 1996, 7, 1117-1122; Tetrahedron: asymmetry, 2002 , 13, 2277-2282). It is obtained by asymmetric synthesis of the corresponding aldehyde (WO2004 / 110976; J.Org.Chem.1992, 57, 1237-1241). [0003] In the existing...

Claims

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Application Information

Patent Timeline
15 Apr 2009
Publication
CN101407465A
IPC
C07C209/88; C07C211/30
Inventors
杨武星; 马建义