Patent ID: 8618312

Claim:
A method for producing a bicyclo[3.1.0]hexane derivative represented by Formula (I) and a salt thereof (in Formula (I), R 1 is (1) â€”OH, (2) â€”Oâ€”R a , or (3) â€”NR b R c , R a is a C 1-6 alkyl group or a C 3-8 cycloalkyl group (said C 1-6 alkyl group or C 3-8 cycloalkyl group being unsubstituted or substituted with one or more C 1-6 alkoxy groups, hydroxy groups, halogens, aryl groups, or heteroaryl groups), R b and R c are identical or different and are each hydrogen, a halogen, a C 1-6 alkyl group, or a C 3-8 cycloalkyl group (said C 1-6 alkyl group or C 3-8 cycloalkyl group being unsubstituted or substituted with one or more hydroxy groups, C 1-6 alkoxy groups, aryl groups, or heteroaryl groups), or R b and R c are bonded to each other and, together with the adjacent nitrogen atom, form a 4- to 7-membered saturated heterocycle (said saturated heterocycle being unsubstituted or substituted with a hydroxy group, a C 1-6 alkyl group, or a C 1-6 alkoxy group), R 2 and R 3 are identical or different and are each hydrogen, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, or a â€”(CH 2 ) m -phenyl group, and m is 0, 1, or 2), said method comprising: (A) converting a compound represented by Formula (II) into a compound represented by Formula (III), wherein the compound represented by Formula (III) is produced by reacting the compound represented by Formula (II) with an acyl group donor in the presence of a microorganism-derived enzyme (R 1 in Formula (II) is as defined in Formula (I)) (in Formula (III), R 1 is as defined in Formula (I), R 4 is hydrogen, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, or a â€”(CH 2 ) n -phenyl group (said C 1-6 alkyl group, C 3-8 cycloalkyl group, or â€”(CH 2 ) n -phenyl group being unsubstituted or substituted with one or more halogens, hydroxy groups, C 1-6 alkyl groups, or C 1-6 alkoxy groups), and n is 0, 1, or 2); (B) converting said compound represented by Formula (III) into a compound represented by Formula (IV) (R 1 and R 4 in Formula (IV) are as defined in Formula (I) and Formula (III)); (C) reacting said compound represented by Formula (IV) with a compound represented by Formula (V) to obtain a compound represented by Formula (VI) (in Formula (V), R 2 and R 3 are as defined in Formula (I), R 5 is hydrogen or Siâ€”(R 6 )(R 7 )(R 8 ), and R 6 , R 7 and R 8 are identical or different and are each a C 1-6 alkyl group or a phenyl group) (R 1 , R 2 , and R 3 in Formula (VI) are as defined in Formula (I) and R 4 is as defined in Formula (III)), and (D) converting said compound represented by Formula (VI) into the compound represented by Formula (I).