2-[(4-methoxyphenyl)methylsulfanyl]ethanamine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Methoxybenzyl chloride (15.6 g) was reacted with 2-aminoethanethiol (7.7 g) in methanol and sodium methoxide, to afford of 2-(4-methoxybezyl-sulfanyl)-ethylamine (1) (18.8 g). One half of this material was taken in dichloromethane (cooling bath 0° C.). Chloroacetyl chloride in the same solvent, was added slowly with stirring, followed by an equivalent of triethyl amine to produce 2-chloro N-[2-(4-methoxybenzyl-sulfanyl)-ethyl]acetamide (2) in a 94% yield. Compound 2 was reacted with an equivalent amount of 1 in refluxing acetonitrile for 6 hrs to provide N-[-2-(4-methoxy-benzylsulfanyl)-ethyl]-2-[2-(4-methoxy-benzylsulfanyl)-ethylamino]-acetamide (3) (40.4 g). Compound 3 was reduced with lithium aluminium hydride (LAH) to yield 4 in 85%.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Methoxybenzyl chloride (15.6 g) was reacted with 2-aminoethanethiol (7.7 g) in methanol and sodium methoxide, to afford of 2-(4-methoxybezyl-sulfanyl)-ethylamine (1) (18.8 g). One half of this material was taken in dichloromethane (cooling bath 0° C.). Chloroacetyl chloride in the same solvent, was added slowly with stirring, followed by an equivalent of triethyl amine to produce 2-chloro N-[2-(4-methoxybenzyl-sulfanyl)-ethyl]acetamide (2) in a 94% yield. Compound 2 was reacted with an equivalent amount of 1 in refluxing acetonitrile for 6 hrs to provide N-[-2-(4-methoxy-benzylsulfanyl)-ethyl]-2-[2-(4-methoxy-benzylsulfanyl)-ethylamino]-acetamide (3) (40.4 g). Compound 3 was reduced with lithium aluminium hydride (LAH) to yield 4 in 85%.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Methoxybenzyl chloride (15.6 g) was reacted with 2-aminoethanethiol (7.7 g) in methanol and sodium methoxide, to afford of 2-(4-methoxybezyl-sulfanyl)-ethylamine (1) (18.8 g). One half of this material was taken in dichloromethane (cooling bath 0° C.). Chloroacetyl chloride in the same solvent, was added slowly with stirring, followed by an equivalent of triethyl amine to produce 2-chloro N-[2-(4-methoxybenzyl-sulfanyl)-ethyl]acetamide (2) in a 94% yield. Compound 2 was reacted with an equivalent amount of 1 in refluxing acetonitrile for 6 hrs to provide N-[-2-(4-methoxy-benzylsulfanyl)-ethyl]-2-[2-(4-methoxy-benzylsulfanyl)-ethylamino]-acetamide (3) (40.4 g). Compound 3 was reduced with lithium aluminium hydride (LAH) to yield 4 in 85%.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a dry nitrogen atmosphere, a mixture of 8.0 grams (0.041 mole) of 2-[(4methoxyphenyl)-methylthio]ethylamine (known compound), 5.7 grams (0.041 mole) of 6-chloropyridine-3-carbaldehyde and 9.7 grams (0.081 mole) of magnesium sulfate in 160 mL of 1,2-dichloroethane was stirred at ambient temperature for about five hours. Sodium triacetoxyborohydride (12.9 grams, 0.061 mole) was added and the reaction mixture stirred at ambient temperature for about 18 hours. After this time 200 mL of an aqueous 5% sodium carbonate solution was added and the mixture stirred for two hours. The mixture was filtered and the filter cake rinsed with methylene chloride. The filtrate and rinse were combined and extracted with three portions of methylene chloride. The combined extracts were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a yellow oil. The oil was subjected to several column chromatography purifications on silica gel, combining the appropriate fractions and concentrating prior to the next purification, eluting with mixtures of methylene chloride and methanol. The third chromatography purification provided 9.39 grams of [(6-chloro(3-pyridyl))methyl]{2-[(4-methoxyphenyl)methylthio]ethyl}amine as an oil. The NMR spectrum was consistent with the proposed structure. the reaction mixture stirred at ambient temperature for about 18 hours the mixture stirred for two hours The mixture was filtered the filter cake rinsed with methylene chloride The filtrate and rinse extracted with three portions of methylene chloride The combined extracts were dried with sodium sulfate filtered The filtrate was concentrated under reduced pressure to a yellow oil concentrating to the next purification eluting with mixtures of methylene chloride and methanol The third chromatography purification

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The [1RS-(2-exo,3-exo)]-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl chloride 21 obtained in Example 17 was dissolved in 10 ml of dichloromethane, and the solution was cooled to −10° C. A solution of 197 mg (1 mmol) of 4-methoxybenzylthioethylamine in 10 ml of dichloromethane and then 0.28 ml (2 mmol) of triethylamine were added thereto under nitrogen, and the resulting mixture was stirred at room temperature for 6 hours. Thereafter, 20 ml of water was added thereto and the desired compound was extracted three times with dichloromethane. The combined organic layer was dried over sodium sulfate and then distilled to remove the solvent. The oil thus obtained was purified by silica gel column chromatography (eluent: ethyl acetate/methanol/aqueous ammonia=8.5/1/0.5) to obtain [1RS-(2-exo,3-exo)]-3-(4-chlorophenyl)-N-[2-[S-(4-methoxybenzyl)thio]ethyl]-8-methyl-8-azabicyclo[3.2.])-octane-2-carboxamide as an oil. the desired compound was extracted three times with dichloromethane The combined organic layer was dried over sodium sulfate distilled to remove the solvent The oil thus obtained was purified by silica gel column chromatography (eluent: ethyl acetate/methanol/aqueous ammonia=8.5/1/0.5)