2-chloroethoxymethylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 4-Amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide dihydrochloride (6 g) as a starting compound, potassium carbonate (10.1 g) and 2-benzyloxyethyl chloride (3 g) were reacted and treated in the same manner as in Example 199 to give 6.36 g of 4-amino-N-((1-(2-benzyloxyethyl)piperidin-4-yl)methyl)-5-chloro-2-methoxybenzamide, m.p. 123°-125° C. treated in the same manner as in Example 199

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

Procedure: To a solution of 2-benzyloxyethanol (11.7 g) and pyridine (6.08 g) in dichloromethane (50 ml) was added thionyl chloride (6.7 ml) under ice-cooling, and the resulting mixture was stirred at refluxing temperature for 2.5 hr. Ice-water was added to the reaction mixture, and the organic layer was washed with water and dried. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform) to give 10.3 g of 2-benzyloxyethyl chloride. cooling at refluxing temperature for 2.5 hr the organic layer was washed with water dried The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel column chromatography (chloroform)

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

Procedure: A solution of 2-benzyloxy-1-chloroethane (Synthesis, 1990, 495.) (7.2 g, 0.043 mol) and thiourea (3.2 g; 0.043 mol) in 95% ethanol (50 ml) was refluxed for 24 hours. To the reaction mixture, potassium hydroxide (4 g, 0.061 mol) and water (40 ml) were added and they were refluxed for 5 hours. The solvent was then distilled off under reduced pressure. The residue was neutralized with a 10% aqueous solution of sulfuric acid, followed by extraction with ethyl ether. The ether solution was washed with water, dried over sodium sulfate and then distilled off under reduced pressure, whereby 2-benzyloxyethanethiol (4.2 g, yield: 59.0%) was obtained as a colorless oil. they were refluxed for 5 hours The solvent was then distilled off under reduced pressure followed by extraction with ethyl ether The ether solution was washed with water dried over sodium sulfate distilled off under reduced pressure

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

Procedure: A solution of 2-benzyloxy-1-chloroethane (Synthesis, 1990, 495.) (7.2 g, 0.043 mol) and thiourea (3.2 g; 0.043 mol) in 95% ethanol (50 ml) was refluxed for 24 hours. To the reaction mixture, potassium hydroxide (4 g, 0.061 mol) and water (40 ml) were added and they were refluxed for 5 hours. The solvent was then distilled off under reduced pressure. The residue was neutralized with a 10% aqueous solution of sulfuric acid, followed by extraction with ethyl ether. The ether solution was washed with water, dried over sodium sulfate and then distilled off under reduced pressure, whereby 2-benzyloxyethanethiol (4.2 g, yield: 59.0%) was obtained as a colorless oil. they were refluxed for 5 hours The solvent was then distilled off under reduced pressure followed by extraction with ethyl ether The ether solution was washed with water dried over sodium sulfate distilled off under reduced pressure

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

Procedure: Following the procedure of Example 102 and using (3aRS,7aRS)-7,7-diphenyl-2-(2-hydroxyphenylacetyl)-4-perhydroisoindolone and 1-benzyloxy-2-chloroethane as starting materials, (3aRS,7aRS)-7,7-diphenyl-2-{2-[2-(2-hydroxyethoxy)phenyl]acetyl}-4-perhydroisoindolone (0.5 g) is obtained in the form of white crystals melting at 150° C.

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

Procedure: 4-Amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide dihydrochloride (6 g) as a starting compound, potassium carbonate (10.1 g) and 2-benzyloxyethyl chloride (3 g) were reacted and treated in the same manner as in Example 199 to give 6.36 g of 4-amino-N-((1-(2-benzyloxyethyl)piperidin-4-yl)methyl)-5-chloro-2-methoxybenzamide, m.p. 123°-125° C. treated in the same manner as in Example 199

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

Procedure: To a solution of 2-benzyloxyethanol (11.7 g) and pyridine (6.08 g) in dichloromethane (50 ml) was added thionyl chloride (6.7 ml) under ice-cooling, and the resulting mixture was stirred at refluxing temperature for 2.5 hr. Ice-water was added to the reaction mixture, and the organic layer was washed with water and dried. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform) to give 10.3 g of 2-benzyloxyethyl chloride. cooling at refluxing temperature for 2.5 hr the organic layer was washed with water dried The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel column chromatography (chloroform)

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

Procedure: A solution of 2-benzyloxy-1-chloroethane (Synthesis, 1990, 495.) (7.2 g, 0.043 mol) and thiourea (3.2 g; 0.043 mol) in 95% ethanol (50 ml) was refluxed for 24 hours. To the reaction mixture, potassium hydroxide (4 g, 0.061 mol) and water (40 ml) were added and they were refluxed for 5 hours. The solvent was then distilled off under reduced pressure. The residue was neutralized with a 10% aqueous solution of sulfuric acid, followed by extraction with ethyl ether. The ether solution was washed with water, dried over sodium sulfate and then distilled off under reduced pressure, whereby 2-benzyloxyethanethiol (4.2 g, yield: 59.0%) was obtained as a colorless oil. they were refluxed for 5 hours The solvent was then distilled off under reduced pressure followed by extraction with ethyl ether The ether solution was washed with water dried over sodium sulfate distilled off under reduced pressure

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

Procedure: A solution of 2-benzyloxy-1-chloroethane (Synthesis, 1990, 495.) (7.2 g, 0.043 mol) and thiourea (3.2 g; 0.043 mol) in 95% ethanol (50 ml) was refluxed for 24 hours. To the reaction mixture, potassium hydroxide (4 g, 0.061 mol) and water (40 ml) were added and they were refluxed for 5 hours. The solvent was then distilled off under reduced pressure. The residue was neutralized with a 10% aqueous solution of sulfuric acid, followed by extraction with ethyl ether. The ether solution was washed with water, dried over sodium sulfate and then distilled off under reduced pressure, whereby 2-benzyloxyethanethiol (4.2 g, yield: 59.0%) was obtained as a colorless oil. they were refluxed for 5 hours The solvent was then distilled off under reduced pressure followed by extraction with ethyl ether The ether solution was washed with water dried over sodium sulfate distilled off under reduced pressure

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

Procedure: Following the procedure of Example 102 and using (3aRS,7aRS)-7,7-diphenyl-2-(2-hydroxyphenylacetyl)-4-perhydroisoindolone and 1-benzyloxy-2-chloroethane as starting materials, (3aRS,7aRS)-7,7-diphenyl-2-{2-[2-(2-hydroxyethoxy)phenyl]acetyl}-4-perhydroisoindolone (0.5 g) is obtained in the form of white crystals melting at 150° C.

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

Procedure: 4-Amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide dihydrochloride (6 g) as a starting compound, potassium carbonate (10.1 g) and 2-benzyloxyethyl chloride (3 g) were reacted and treated in the same manner as in Example 199 to give 6.36 g of 4-amino-N-((1-(2-benzyloxyethyl)piperidin-4-yl)methyl)-5-chloro-2-methoxybenzamide, m.p. 123°-125° C. treated in the same manner as in Example 199