Lithiation of 6-methoxybenzothiophene (I), followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III), which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1). In a related procedure, the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2). Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2). Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1). Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX). The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).

Lithiation of 6-methoxybenzothiophene (I), followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III), which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1). In a related procedure, the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2). Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2). Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1). Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX). The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).

Lithiation of 6-methoxybenzothiophene (I), followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III), which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1). In a related procedure, the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2). Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2). Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1). Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX). The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).

The condensation of 1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidine (I) with 2-chloroethyl isocyanate (II) gives 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)urea (III). The nitrosation of (III) with dinitrogen tetraoxide in methylene chloride yields SLCNU.

The nitrosation of (IV) with dinitrogen tetraoxide in methylene chloride affords (V), which is condensed with (I) to yield SLCNU.

Lithiation of 6-methoxybenzothiophene (I), followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III), which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1). In a related procedure, the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2). Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2). Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1). Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX). The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).

Lithiation of 6-methoxybenzothiophene (I), followed by condensation with cyclohexanone (II) provides the hydroxycyclohexyl benzothiophene (III), which is further dehydrated to the cyclohexenyl analogue (IV) under acidic conditions (1). In a related procedure, the cyclohexenyl benzothiophene (IV) is prepared by condensation of the lithiated derivative of (I) with cyclohexenyl triflate (V) in the presence of ZnCl2 and Pd(PPh3)4 (2). Catalytic hydrogenation of olefin (IV) over Pd/C leads to the cyclohexyl benzothiophene (VI) (1,2). Subsequent Friedel-Crafts acylation of (VI) with 4-(2-chloroethoxy)benzoyl chloride (VII) yields ketone (VIII) (1). Displacement of the chloride group in (VIII) with piperidine furnishes the piperidinyl ethoxy derivative (IX). The methyl ether (IX) is finally cleaved by treatment with AlCl3 and EtSH to produce the target phenol derivative (1,3-5).

In an alternative procedure, condensation of 4-methoxybenzaldehyde (I) with N,N-dimethyl thioformamide in the presence of LDA, followed by treatment with methanesulfonic acid leads to 6-methoxy-2-(dimethylamino)benzothiophene (II), which is subsequently acylated with 4-[2-(-1piperidino)ethoxy]benzoyl chloride (III) in hot chlorobenzene to provide the 3-benzoyl benzothiophene (IV) (6). The dimethylamino group in (IV) is displaced with cyclohexylmagnesium bromide (V) yielding (VI). Finally, methyl ether (VI) cleavage by means of AlCl3 and EtSH gives rise to the title compound (6,7).

In an alternative procedure, condensation of 4-methoxybenzaldehyde (I) with N,N-dimethyl thioformamide in the presence of LDA, followed by treatment with methanesulfonic acid leads to 6-methoxy-2-(dimethylamino)benzothiophene (II), which is subsequently acylated with 4-[2-(-1piperidino)ethoxy]benzoyl chloride (III) in hot chlorobenzene to provide the 3-benzoyl benzothiophene (IV) (6). The dimethylamino group in (IV) is displaced with cyclohexylmagnesium bromide (V) yielding (VI). Finally, methyl ether (VI) cleavage by means of AlCl3 and EtSH gives rise to the title compound (6,7).