Intermediates for the production of optically active cyclopropylamine derivatives and process for the production of the intermediates

1. A process for producing an optically active compound represented by formula (4), or a salt thereof,

wherein R 1 represents a protecting group, the process comprising:

reacting a compound of formula (1)

with an alkylsulfonyl chloride or an arylsulfonyl chloride, in the presence of a base, to form a compound of formula (2)

wherein X represents an alkylsulfonyl group or an arylsulfonyl group,

reacting the compound of formula (2) with a cyanating agent to form a compound of formula (3)

reacting the compound of formula (3) with an alkyl metal compound, a titanium (IV) reagent, and optionally a Lewis acid, to form the compound of formula (4), or a salt thereof.

2. The process according to claim 1 , wherein the titanium(IV) reagent is a titanium(IV) alkoxide.

3. The process according to claim 1 , wherein the titanium(IV) reagent is titanium(IV) tetraisopropoxide, methyltitanium(IV) triisopropoxide, or chlorotitanium(IV) triisopropoxide.

4. The process according to any one of claims 1 to 3 , wherein the alkylmetal compound is an ethylmetal compound.

5. The process according to any one of claims 1 to 3 , wherein the alkylmetal compound is an alkyl Grignard reagent or a dialkylzinc.

6. The process according to claim 5 , wherein the alkyl Grignard reagent is an ethyl Grignard reagent.

7. The process according to claim 6 , wherein the ethyl Grignard reagent is ethylmagnesium chloride or ethylmagnesium bromide.

8. The process according to claim 7 , wherein the ethyl Grignard reagent is ethylmagnesium bromide.

9. The process according to any one of claims 1 to 3 , wherein the alkylmetal compound is diethylzinc.

10. The process of claim 1 , comprising reacting the compound of formula (3) with an alkyl metal compound, a titanium (IV) reagent, and a Lewis acid, to form the compound of formula (4), or a salt thereof.

11. The process of claim 1 ,

wherein the alkylsulfonyl chloride is selected from the group consisting of methanesulfonyl chloride and trifluoromethanesulfonyl chloride;

wherein the arylsulfonyl chloride is selected from the group consisting of phenylsulfonyl chloride and p-toluenesulfonyl chloride;

wherein the cyanating agent is selected from the group consisting of sodium cyanide, potassium cyanide, and tetrabutylammonium cyanide;

wherein the titanium (IV) reagent is selected from the group consisting of titanium (IV) tetraisopropoxide, methyltitanium (IV) triisopropoxide, and chlorotitanium (IV) triisopropoxide;

wherein the Lewis acid is selected from the group consisting of trifluoroboron, aluminum chloride, and lithium iodide;

wherein the alkyl metal compound is selected from the group consisting of ethyl magnesium chloride, ethyl magnesium bromide, and diethyl zinc; and

wherein the protecting group is selected from the group consisting of tert-butoxycarbonyl, methoxycarbonyl, ethoxycarbonyl, 2,2,2-trichlorocarbonyl, benzyloxycarbonyl, paramethoxybenzyloxycarbonyl, paranitrobenzyloxycarbonyl, formyl, acetyl, propanoyl, tert-butyloyl, pivaloyl, benzoyl, benzyl, α-methylbenzyl, trityl, diphenylmethyl(benzhydryl), paranitrobenzyl, paramethoxybenzyl, phenethyl, methoxyphenyl, and tert-butoxycarbonylamino.

12. The process of claim 11 , wherein the base is triethylamine.

13. The process of claim 11 , wherein the compound of formula (3) is reacted with the alkyl metal compound the titanium (IV) reagant and the Lewis acid.

14. The process of claim 11 , wherein the compound of formula (1) is reacted with the arylsulfonyl chloride.

15. The process of claim 11 , wherein the compound of formula (1) is reacted with the alkylsulfonyl chloride.