2-(1-benzylpiperidin-4-yl)ethanol

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

Procedure: To a solution of 3 mL (34.4 mmol) of oxalyl chloride in 80 mL of CH2Cl2 at −78° C. was added a solution of 4.9 mL (68.8 mmol) of DMSO in 5 mL of CH2Cl2. After stirring for 10 min, a solution of 4 g (18.24 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical) in 20 mL of CH2Cl2 was added dropwise. After 30 min, 12 mL (86.1 mmol) of Et3N was added and the reaction mixture was allowed to warm to rt over a period of 30 min. To the reaction mixture was added 100 mL of H2O and it was extracted with CH2Cl2. The combined organic fractions were washed with sat'd NaCl solution, and dried over MgSO4 and filtered. The filtrate was concentrated to give 4 g of the title compound. After 30 min was extracted with CH2Cl2 The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered The filtrate was concentrated

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

Procedure: To a solution of 1.5 g (6.84 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical), 3.8 g (34.2 mmol) of 4-fluorophenol and 3.6 g (13.7 mmol) of triphenylphosphine in 25 mL of ether at 0° C. was slowly added dropwise 2.15 mL (13.7 mmol) of diethylazodicarboxylate (DEAD). The reaction mixture was allowed to warm to rt and was stirred for 12 h. To the reaction mixture was added 70 mL of ether and it was filtered through a thin pad of celite. The filtrate was washed with sat'd Na2CO3 solution and sat's NaCl solution. It was dried over MgSO4, filtered and the filtrate concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1) to give 0.85 g of the title compound. was filtered through a thin pad of celite The filtrate was washed with sat'd Na2CO3 solution It was dried over MgSO4 filtered the filtrate concentrated The residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1)

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

Procedure: To a stirred and cooled (-10° C.) mixture of 19.6 parts of triphenyl phosphine and 54 parts of tetrahydrofuran were added portionwise 13.7 parts of diethyl diazenedicarboxylate (exothermic reaction). Upon completion, stirring was continued for 15 minutes and then a solution of 16.5 parts of 1-(phenylmethyl)-4-piperidineethanol and 12.5 parts of ethyl 4-hydroxybenzoate in 54 parts of tetrahydrofuran was added dropwise at a temperature between 0° and -5° C. After complete addition, the whole was stirred overnight at room temperature and then evaporated. Water was added to the residue and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was dissolved in 2,2'-oxybispropane and allowed to crystallize. The precipitate was filtered off and the filtrate was evaporated. The residue was converted into the (Z)-2-butenedioate salt in 280 parts of 2-propanol. The salt was filtered off and dried, yielding 15 parts (42%) of ethyl 4-[2-[ 1-(phenylmethyl)-4-piperidinyl]ethoxy]benzoate (Z)-2-butenedioate(1:1); mp. 142.0° C. (int. 50). cooled Upon completion, stirring After complete addition the whole was stirred overnight at room temperature evaporated Water was added to the residue the product was extracted with dichloromethane The extract was dried filtered evaporated The residue was dissolved in 2,2'-oxybispropane to crystallize The precipitate was filtered off the filtrate was evaporated The salt was filtered off dried

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

Procedure: To a stirred and cooled (-10° C.) mixture of 19.6 parts of triphenyl phosphine and 54 parts of tetrahydrofuran were added portionwise 13.7 parts of diethyl diazenedicarboxylate (exothermic reaction). Upon completion, stirring was continued for 15 minutes and then a solution of 16.5 parts of 1-(phenylmethyl)-4-piperidineethanol and 12.5 parts of ethyl 4-hydroxybenzoate in 54 parts of tetrahydrofuran was added dropwise at a temperature between 0° and -5° C. After complete addition, the whole was stirred overnight at room temperature and then evaporated. Water was added to the residue and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was dissolved in 2,2'-oxybispropane and allowed to crystallize. The precipitate was filtered off and the filtrate was evaporated. The residue was converted into the (Z)-2-butenedioate salt in 280 parts of 2-propanol. The salt was filtered off and dried, yielding 15 parts (42%) of ethyl 4-[2-[ 1-(phenylmethyl)-4-piperidinyl]ethoxy]benzoate (Z)-2-butenedioate(1:1); mp. 142.0° C. (int. 50). cooled Upon completion, stirring After complete addition the whole was stirred overnight at room temperature evaporated Water was added to the residue the product was extracted with dichloromethane The extract was dried filtered evaporated The residue was dissolved in 2,2'-oxybispropane to crystallize The precipitate was filtered off the filtrate was evaporated The salt was filtered off dried

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

Procedure: To a stirred and cooled (-10° C.) mixture of 19.6 parts of triphenyl phosphine and 54 parts of tetrahydrofuran were added portionwise 13.7 parts of diethyl diazenedicarboxylate (exothermic reaction). Upon completion, stirring was continued for 15 minutes and then a solution of 16.5 parts of 1-(phenylmethyl)-4-piperidineethanol and 12.5 parts of ethyl 4-hydroxybenzoate in 54 parts of tetrahydrofuran was added dropwise at a temperature between 0° and -5° C. After complete addition, the whole was stirred overnight at room temperature and then evaporated. Water was added to the residue and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was dissolved in 2,2'-oxybispropane and allowed to crystallize. The precipitate was filtered off and the filtrate was evaporated. The residue was converted into the (Z)-2-butenedioate salt in 280 parts of 2-propanol. The salt was filtered off and dried, yielding 15 parts (42%) of ethyl 4-[2-[ 1-(phenylmethyl)-4-piperidinyl]ethoxy]benzoate (Z)-2-butenedioate(1:1); mp. 142.0° C. (int. 50). cooled Upon completion, stirring After complete addition the whole was stirred overnight at room temperature evaporated Water was added to the residue the product was extracted with dichloromethane The extract was dried filtered evaporated The residue was dissolved in 2,2'-oxybispropane to crystallize The precipitate was filtered off the filtrate was evaporated The salt was filtered off dried

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

Procedure: To a solution of 3 mL (34.4 mmol) of oxalyl chloride in 80 mL of CH2Cl2 at −78° C. was added a solution of 4.9 mL (68.8 mmol) of DMSO in 5 mL of CH2Cl2. After stirring for 10 min, a solution of 4 g (18.24 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical) in 20 mL of CH2Cl2 was added dropwise. After 30 min, 12 mL (86.1 mmol) of Et3N was added and the reaction mixture was allowed to warm to rt over a period of 30 min. To the reaction mixture was added 100 mL of H2O and it was extracted with CH2Cl2. The combined organic fractions were washed with sat'd NaCl solution, and dried over MgSO4 and filtered. The filtrate was concentrated to give 4 g of the title compound. After 30 min was extracted with CH2Cl2 The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered The filtrate was concentrated

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

Procedure: To a solution of 3 mL (34.4 mmol) of oxalyl chloride in 80 mL of CH2Cl2 at −78° C. was added a solution of 4.9 mL (68.8 mmol) of DMSO in 5 mL of CH2Cl2. After stirring for 10 min, a solution of 4 g (18.24 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical) in 20 mL of CH2Cl2 was added dropwise. After 30 min, 12 mL (86.1 mmol) of Et3N was added and the reaction mixture was allowed to warm to rt over a period of 30 min. To the reaction mixture was added 100 mL of H2O and it was extracted with CH2Cl2. The combined organic fractions were washed with sat'd NaCl solution, and dried over MgSO4 and filtered. The filtrate was concentrated to give 4 g of the title compound. After 30 min was extracted with CH2Cl2 The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered The filtrate was concentrated

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

Procedure: To a solution of 1.5 g (6.84 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical), 3.8 g (34.2 mmol) of 4-fluorophenol and 3.6 g (13.7 mmol) of triphenylphosphine in 25 mL of ether at 0° C. was slowly added dropwise 2.15 mL (13.7 mmol) of diethylazodicarboxylate (DEAD). The reaction mixture was allowed to warm to rt and was stirred for 12 h. To the reaction mixture was added 70 mL of ether and it was filtered through a thin pad of celite. The filtrate was washed with sat'd Na2CO3 solution and sat's NaCl solution. It was dried over MgSO4, filtered and the filtrate concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1) to give 0.85 g of the title compound. was filtered through a thin pad of celite The filtrate was washed with sat'd Na2CO3 solution It was dried over MgSO4 filtered the filtrate concentrated The residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1)

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

Procedure: To a solution of 1.5 g (6.84 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical), 3.8 g (34.2 mmol) of 4-fluorophenol and 3.6 g (13.7 mmol) of triphenylphosphine in 25 mL of ether at 0° C. was slowly added dropwise 2.15 mL (13.7 mmol) of diethylazodicarboxylate (DEAD). The reaction mixture was allowed to warm to rt and was stirred for 12 h. To the reaction mixture was added 70 mL of ether and it was filtered through a thin pad of celite. The filtrate was washed with sat'd Na2CO3 solution and sat's NaCl solution. It was dried over MgSO4, filtered and the filtrate concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1) to give 0.85 g of the title compound. was filtered through a thin pad of celite The filtrate was washed with sat'd Na2CO3 solution It was dried over MgSO4 filtered the filtrate concentrated The residue was purified by chromatography (silica, hexanes: ethyl acetate, 4:1)

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

Procedure: To a stirred and cooled (-10° C.) mixture of 19.6 parts of triphenyl phosphine and 54 parts of tetrahydrofuran were added portionwise 13.7 parts of diethyl diazenedicarboxylate (exothermic reaction). Upon completion, stirring was continued for 15 minutes and then a solution of 16.5 parts of 1-(phenylmethyl)-4-piperidineethanol and 12.5 parts of ethyl 4-hydroxybenzoate in 54 parts of tetrahydrofuran was added dropwise at a temperature between 0° and -5° C. After complete addition, the whole was stirred overnight at room temperature and then evaporated. Water was added to the residue and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was dissolved in 2,2'-oxybispropane and allowed to crystallize. The precipitate was filtered off and the filtrate was evaporated. The residue was converted into the (Z)-2-butenedioate salt in 280 parts of 2-propanol. The salt was filtered off and dried, yielding 15 parts (42%) of ethyl 4-[2-[ 1-(phenylmethyl)-4-piperidinyl]ethoxy]benzoate (Z)-2-butenedioate(1:1); mp. 142.0° C. (int. 50). cooled Upon completion, stirring After complete addition the whole was stirred overnight at room temperature evaporated Water was added to the residue the product was extracted with dichloromethane The extract was dried filtered evaporated The residue was dissolved in 2,2'-oxybispropane to crystallize The precipitate was filtered off the filtrate was evaporated The salt was filtered off dried

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

Procedure: To a stirred and cooled (-10° C.) mixture of 19.6 parts of triphenyl phosphine and 54 parts of tetrahydrofuran were added portionwise 13.7 parts of diethyl diazenedicarboxylate (exothermic reaction). Upon completion, stirring was continued for 15 minutes and then a solution of 16.5 parts of 1-(phenylmethyl)-4-piperidineethanol and 12.5 parts of ethyl 4-hydroxybenzoate in 54 parts of tetrahydrofuran was added dropwise at a temperature between 0° and -5° C. After complete addition, the whole was stirred overnight at room temperature and then evaporated. Water was added to the residue and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was dissolved in 2,2'-oxybispropane and allowed to crystallize. The precipitate was filtered off and the filtrate was evaporated. The residue was converted into the (Z)-2-butenedioate salt in 280 parts of 2-propanol. The salt was filtered off and dried, yielding 15 parts (42%) of ethyl 4-[2-[ 1-(phenylmethyl)-4-piperidinyl]ethoxy]benzoate (Z)-2-butenedioate(1:1); mp. 142.0° C. (int. 50). cooled Upon completion, stirring After complete addition the whole was stirred overnight at room temperature evaporated Water was added to the residue the product was extracted with dichloromethane The extract was dried filtered evaporated The residue was dissolved in 2,2'-oxybispropane to crystallize The precipitate was filtered off the filtrate was evaporated The salt was filtered off dried

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

Procedure: To a solution of 3 mL (34.4 mmol) of oxalyl chloride in 80 mL of CH2Cl2 at −78° C. was added a solution of 4.9 mL (68.8 mmol) of DMSO in 5 mL of CH2Cl2. After stirring for 10 min, a solution of 4 g (18.24 mmol) of 1-benzyl-4-(2-hydroxy-1-ethyl)piperidine (Acros Chemical) in 20 mL of CH2Cl2 was added dropwise. After 30 min, 12 mL (86.1 mmol) of Et3N was added and the reaction mixture was allowed to warm to rt over a period of 30 min. To the reaction mixture was added 100 mL of H2O and it was extracted with CH2Cl2. The combined organic fractions were washed with sat'd NaCl solution, and dried over MgSO4 and filtered. The filtrate was concentrated to give 4 g of the title compound. After 30 min was extracted with CH2Cl2 The combined organic fractions were washed with sat'd NaCl solution dried over MgSO4 filtered The filtrate was concentrated