Method for producing optically active 2-(2-fluorobiphenyl-4-yl) propanoic acid

A process for producing a compound of formula [4]

• comprising:
• (a) preparing an organometallic reagent by reacting a compound of formula [1]
• with magnesium;
• and
• (b) reacting a compound of formula [2]
• with the organometallic reagent prepared in (a) in the presence of a catalytic amount of a nickel compound and a catalytic amount of an optically active compound of formula [3]
• to obtain the compound of formula [4];
• wherein
• X1 represents a halogen atom;
• X2 represents a halogen atom;
• R1 represents tert-butyldiphenylsilyl, C1-6 alkyl, C2-6 alkenyl, C3-8 cycloalkyl, phenyl, or benzyl optionally substituted with one or two groups selected from group A1of substituents;
• R2 and R3 independently represent C1-6 alkyl, or R2, R3 and the carbon atom adjacent to said substituents may, taken together, form C3-6 cycloalkane;
• R4 and R5 independently represent C1-6 alkyl, benzyl, phenethyl, or phenyl optionally substituted with one or two groups selected from group A2 of substituents, wherein
• group A1 of substituents consists of C1-6 alkyl and phenyl, and
• group A2 of substituents consists of a halogen atom, C1-6 alkyl, halo-C3-6 alkyl, C1-6 alkoxy, halo-C1-6 alkoxy, and phenyl.