Method for producing bicyclic compound

1. A method for producing a compound represented by formula (G) or a salt thereof:

wherein, R 1 represents a C1-6 alkyl group optionally substituted with a hydroxyl group or a C1-4 alkoxy group, Z represents (1) —(CH 2 ) m —, (2) —(CH 2 ) n —CH═CH—, or (3) —(CH 2 ) p -A-CH 2 —, A represents an oxygen atom, or a sulfur atom, m represents an integer of 1 to 6, n represents an integer of 1 to 4, and p represents an integer of 1 to 4, and T 1 represents (1) a p-phenybenzoyl group, (2) a methyl group, (3) a trityl group, (4) a methoxymethyl group, (5) a 1-ethoxyethyl group, (6) a methoxyethoxymethyl group, (7) a benzyloxymethyl group, (8) a trimethylsilyl group, (9) a triethylsilyl group, (10) a t-butyldimethylsilyl group, (11) a t-butyldiphenylsilyl group, (12) a triisopropylsilyl group, (13) a benzyl group, (14) a p-methoxybenzyl group, (15) an acetyl group, (16) a pivaloyl group, (17) a benzoyl group, (18) an allyloxycarbonyl group, (19) a 2,2,2-trichloroethoxycarbonyl group, (20) a t-butoxycarbonyl group, (21) an allyl group, or (22) a tosyl group,

the method comprising the following steps (i) to (vi):

step (i): subjecting a compound represented by formula (A):

wherein, T 2 represents a benzyl group, and other symbols represent the same meanings as those described above,

to a reduction reaction to produce a compound represented by formula (B):

wherein, all symbols represent the same meanings as those described above,

or a salt thereof;

step (ii): subjecting the compound represented by formula (B) obtained in the step (i) or a salt thereof to a reaction in an organic solvent, in the presence of a base using a Wittig reagent to produce a compound represented by formula (C):

wherein, all symbols represent the same meanings as those described above,

or a salt thereof;

step (iii): subjecting the compound represented by the formula (C) obtained in the step (ii) or a salt thereof and a compound represented by formula (a):

wherein, X represents a halogen atom, a tosyloxy (TsO) group, or a mesyloxy (MsO) group, and other symbols represent the same meanings as those described above,

to an alkylation reaction to produce a compound represented by formula (D):

wherein, all symbols represent the same meanings as those described above;

step (iv): subjecting the compound represented by the formula (D) obtained in the step (iii) to a metathesis reaction to produce a compound represented by formula (E):

wherein, all symbols represent the same meanings as those described above;

step (v): subjecting the compound represented by the formula (E) obtained in the step (iv) to an asymmetric reduction reaction to produce a compound represented by formula (F):

wherein, all symbols represent the same meanings as those described above; and

step (vi): subjecting the compound represented by the formula (F) obtained in the step (v) to a deprotection reaction to produce the compound represented by the formula (G) or a salt thereof.

2. A method for producing a compound represented by formula (K):

wherein, Y represents —CH 2 —, —O— or —S—, represents a C3-10 carbocycle or a 3- to 10-membered heterocycle optionally substituted with 1 to 5 substituents selected from the group consisting of (1) a halogen atom, (2) CF 3 , (3) OCF 3 , (4) a C1-4 alkoxy group, (5) a C1-4 alkyl group, (6) a hydroxyl group, and (7) a nitrile group, R 1 represents a C1-6 alkyl group optionally substituted with a hydroxyl group or a C1-4 alkoxy group, Z represents (1) —(CH 2 ) m —, (2) —(CH 2 ) n —CH═CH—, or (3) —(CH 2 ) p -A-CH 2 —, A represents an oxygen atom, or a sulfur atom, m represents an integer of 1 to 6, n represents an integer of 1 to 4, and p represents an integer of 1 to 4,

the method comprising:

producing a compound represented by formula (G) or a salt thereof from a compound represented by formula (A) according to steps (i) to (vi):

wherein, T 1 represents (1) a p-phenybenzoyl group, (2) a methyl group, (3) a trityl group, (4) a methoxymethyl group, (5) a 1-ethoxyethyl group, (6) a methoxyethoxymethyl group, (7) a benzyloxymethyl group, (8) a trimethylsilyl group, (9) a triethylsilyl group, (10) a t-butyldimethylsilyl group, (11) a t-butyldiphenylsilyl group, (12) a triisopropylsilyl group, (13) a benzyl group, (14) a p-methoxybenzyl group, (15) an acetyl group, (16) a pivaloyl group, (17) a benzoyl group, (18) an allyloxycarbonyl group, (19) a 2,2,2-trichloroethoxycarbonyl group, (20) a t-butoxycarbonyl group, (21) an allyl group, or (22) a tosyl group, and other symbols represent the same meanings as those described above,

step (i): subjecting a compound represented by formula (A):

wherein, T 2 represents a benzyl group, and other symbols represent the same meanings as those described above,

to a reduction reaction to produce a compound represented by formula (B):

wherein, all symbols represent the same meanings as those described above,

or a salt thereof;

step (ii): subjecting the compound represented by formula (B) obtained in the step (i) or a salt thereof to a reaction in an organic solvent, in the presence of a base using a Wittig reagent to produce a compound represented by formula (C):

wherein, all symbols represent the same meanings as those described above,

or a salt thereof;

step (iii): subjecting the compound represented by the formula (C) obtained in the step (ii) or a salt thereof and a compound represented by formula (a):

wherein, X represents a halogen atom, a tosyloxy (Ts0) group, or a mesyloxy (Ms0) group, and other symbols represent the same meanings as those described above,

to an alkylation reaction to produce a compound represented by formula (D):

wherein, all symbols represent the same meanings as those described above;

step (iv): subjecting the compound represented by the formula (D) obtained in the step (iii) to a metathesis reaction to produce a compound represented by formula (E):

wherein, all symbols represent the same meanings as those described above;

step (v): subjecting the compound represented by the formula (E) obtained in the step (iv) to an asymmetric reduction reaction to produce a compound represented by formula (F):

wherein, all symbols represent the same meanings as those described above; and

step (vi): subjecting the compound represented by the formula (F) obtained in the step (v) to a deprotection reaction to produce the compound represented by the formula (G) or a salt thereof;

producing a compound represented by formula (I) or a salt thereof from the compound represented by the formula (G) or a salt thereof according to steps (vii) to (viii):

wherein, all symbols represent the same meanings as those described above,

step (vii): subjecting a compound represented by formula (G):

wherein, all symbols represent the same meanings as those described above, or a salt thereof to an oxidation reaction to produce a compound represented by formula (H):

wherein, all symbols represent the same meanings as those described above; and

step (viii): subjecting the compound represented by the formula (H) obtained in the step (vii) and a compound represented by formula (b):

wherein, R 101 represents a C1-6 alkyl group, and other symbols represent the same meanings as those described above,

to a reaction in an organic solvent, in water, or in a mixed solution thereof, in the presence of a base, in the presence or absence of an additive to produce the compound represented by the formula (I) or a salt thereof; and

producing the compound represented by the formula (K) according to steps (ix) to (x):

step (ix): subjecting a compound represented by formula (I):

wherein, all symbols represent the same meanings as those described above, or a salt thereof, to an asymmetric reduction reaction to produce a compound represented by formula (J) or a salt thereof:

wherein all symbols represent the same meanings as those described above; and

step (x): subjecting the compound represented by the formula (J) or a salt thereof to a deprotection reaction to produce the compound represented by the formula (K).

3. The method according to claim 1 , wherein T 1 is a p-phenybenzoyl group.

4. The method according to claim 2 , wherein the compound represented by the formula (K) is 2-propanyl 4-{(3S,5aR,6R,7R,8aS)-6-[(1E,3R)-4-(2,5-difluorophenoxy)-3-hydroxy-1-buten-1-yl]-7-hydroxyoctahydro-2H-cyclopenta[b]oxepin-3-yl}butanoate.

5. The method according to claim 2 , wherein T 1 is a p-phenybenzoyl group.