METHOD FOR PREPARATION OF CARBAMIC ACID (R)-1-ARYL-2-TETRAZOLYL-ETHYL ESTER

• US 20100323410A1
• Filed: 10/14/2009
• Published: 12/23/2010
• Est. Priority Date: 06/22/2009
• Status: Active Grant

• Current Assignee: SK Biopharmaceuticals Co., Ltd. (SK Inc.)
• Original Assignee: SK Biopharmaceuticals Co., Ltd. (SK Inc.)
• Inventors: Lim, Sang Chul, Lee, Ju Young, Lee, Dong Ho, Cho, Nahm Ryune, Kim, Hui Ho, Uhm, Moo Yong, Lee, Dae Won
• Granted Patent: US 8,501,436 B2
• Time in Patent Office: Days
• US Class Current: 435/121
• CPC Class Codes: C07D 257/04 Five-membered rings
• CPC Class Codes: C12P 17/10 Nitrogen as only ring hetero atom

Abstract

Disclosed is a method for the preparation of carbamic acid (R)-1-aryl-2-tetrazolyl-ethyl ester, comprising the asymmetric reduction of arylketone and the carbamation of alcohol.

Claims

1. A method for preparing carbamic acid aryl-2-tetrazolyl ethyl ester, represented by Chemical Formula 1, comprising:

subjecting an arylketone, represented by Chemical Formula 2, to (R)-selective asymmetric reduction to form an alcohol compound of (R)-configuration, represented by Chemical Formula 3; and

carbamating said alcohol;

2. The method according to claim 1, wherein the (R)-selective asymmetric reduction is achieved by biological asymmetric reduction or chemical asymmetric reduction.

3. The method according to claim 2, wherein the biological asymmetric reduction is carried out in a buffer containing the arylketone of Chemical Formula 2, a microbial strain capable of producing oxidoreductase, and a cosubstrate.

4. The method according to claim 3, wherein the microbial strain is selected from a group consisting of yeasts of Candida genus including Candida parapsilosis and Candida rugosa;

yeasts of Pichia genus including Pichia anomala and Pichia jadinii;

yeasts of Saccharomyces genus including Baker'"'"'s yeast, Saccharomyces cerevisiae and Saccharomyces pastorianus;

yeasts including Rhodotorula mucilaginosa and Trigonopsis variabilis;

bacteria including Klebsiella pneumoniae, Enterobacter cloacae, Erwinia herbicola, Micrococcus luteus, Bacillus stearothermophilus, Rhodococcus erythropolis and Rhodococcus rhodochrous;

fungi including Mucor racemosus and Geotrichum candidum;

and a combination thereof.

5. The method according to claim 2, wherein the chemical asymmetric reduction is achieved with a chiral borane reductant or by asymmetric catalytic hydrogenation or asymmetric catalytic transfer hydrogenation.

6. The method according to claim 5, wherein the chiral borane reductant is (−

)-B-chlorodiisopinocampheylborane or (R)-2-methyl-CBS-oxazaborolidine/borane.

7. The method according to claim 5, wherein the asymmetric catalytic hydrogenation is carried out by reacting the arylketone of Chemical Formula 2 with hydrogen gas in the presence of (R)-bisphosphono-ruthenium(II)-(R,R)-chiral diamine complex catalyst.

8. The method according to claim 5, wherein the asymmetric catalytic transfer hydrogenation is carried out by reacting the arylketone of Chemical Formula 2 with formic acid triethylamine or isopropanol-inorganic base in the presence of a [S,S]-monosulfonatediamine-M(II)-arene complex catalyst system, wherein M represents ruthenium or rhodium.

9. The method according to claim 1, wherein the carbamating step is carried out by reacting the alcohol compound of (R)-configuration of Chemical Formula 3 with inorganic cyanate and an organic acid.

10. The method according to claim 1, wherein the carbamating step is carried out by hydrolyzing a product resulting from reaction between the alcohol compound of (R)-configuration of Chemical formula 3 and an isocyanate compound selected from the group consisting of chlorosulfonic isocyanate, trichloroacetyl isocyanate and trimethylsilyl isocyanate.

11. The method according to claim 1, wherein the carbamating step is carried out by introducing ammonia into a product resulting from reaction between the alcohol compound of (R)-configuration of Chemical formula 3 and a carbonyl compound comprising 1,1′

-carbodiimidazole, carbamoylhalide, disuccinyl carbonate, phosgene, triphosgene or chloroformate.

12. The method according to claim 1, further comprising a crystallizing step after at least one of the (R)-selective asymmetric reduction step and the carbamating step.

13. The method according to claim 12, wherein the crystallizing step comprises:

adding to a reaction product a solubilizing agent selected from among acetone, acetonitrile, tetrahydrofuran, ethylacetate, dichloromethane, chloroform, 1,4-dioxane, a lower alcohol of 1 to 4 carbon atoms and a mixture thereof; and

adding a precipitating agent thereto selected from the group consisting of water, a lower alcohol of 1 to 4 carbon atoms, diethylether, pentane, hexane, cyclohexane, heptane and a mixture thereof.

14. The method according to claim 1, additionally including the step of preparing the arylketone of Chemical Formula 2 is prepared by substitution reaction between an arylketone of the following Chemical Formula 4 with a tetrazole of the following Chemical Formula 5:

15. A method according to claim 14, further comprising a crystallizing step comprising:

adding a solubilizing agent selected from among acetone, acetonitrile, tetrahydrofuran, ethylacetate, dichloromethane, chloroform, 1,4-dioxane, a lower alcohol of 1 to 4 carbon atoms and a mixture thereof to a product obtained by the substitution reaction; and

adding a precipitating agent selected from water, a lower alcohol of 1 to 4 carbon atoms, diethylether, pentane, hexane, cyclohexane, heptanes and a mixture thereof.

16. A method for preparing an alcohol compound, represented by the following Chemical Formula 3, through (R)-selective asymmetric reduction of an arylketone, represented by the following Chemical Formula 2, wherein the (R)-selective asymmetric reduction is achieved by biological asymmetric reduction or chemical asymmetric reduction:

17. The method according to claim 16, wherein the biological asymmetric reduction is carried out in a buffer containing the arylketone of Chemical Formula 2, a microbial strain capable of producing oxidoreductase, and a cosubstrate.

18. The method according to claim 16, wherein the chemical asymmetric reduction is achieved with a chiral borane reductant or by asymmetric catalytic hydrogenation or asymmetric catalytic transfer hydrogenation.