4-(methylsulfanylmethoxy)piperidine

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of alcohol E (1.0 g, 3.1 mmol) and methyl sulfide (1.8 mL, 24.8 mmol) in acetonitrile (31 mL) at 0° C. was added benzoyl peroxide (3.0 g, 12.4 mmol) in four equal portions over 10 min, and the mixture was stirred at 0° C. for 1 h and then at room temperature for 1 h until no E was observed by TLC. The mixture was diluted with ethyl acetate (100 mL), washed with 10% Na2CO3 (100 mL) and then brine (100 mL) and dried over sodium sulfate. The solvent was removed in vacuo to give crude product which was used for the next step without purification. The resulting residue was dissolved in acetonitrile (10 mL) and followed by addition of diethyl amine (6.2 mL, 60 mmol). The mixture was stirred at room temperature for overnight until no starting material was observed by TLC and concentrated in vacuo. The residue was flash chromatographed on silica gel with 5% MeOH/DCM to provide intermediate H (270 mg, yield 54% over two steps). MS (ESI) m/z 162.83 (M+H)+. at room temperature for 1 h until no E was observed by TLC washed with 10% Na2CO3 (100 mL) brine (100 mL) and dried over sodium sulfate The solvent was removed in vacuo to give crude product which was used for the next step without purification The resulting residue was dissolved in acetonitrile (10 mL) The mixture was stirred at room temperature for overnight until no starting material concentrated in vacuo chromatographed on silica gel with 5% MeOH/DCM

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of alcohol E (1.0 g, 3.1 mmol) and methyl sulfide (1.8 mL, 24.8 mmol) in acetonitrile (31 mL) at 0° C. was added benzoyl peroxide (3.0 g, 12.4 mmol) in four equal portions over 10 min, and the mixture was stirred at 0° C. for 1 h and then at room temperature for 1 h until no E was observed by TLC. The mixture was diluted with ethyl acetate (100 mL), washed with 10% Na2CO3 (100 mL) and then brine (100 mL) and dried over sodium sulfate. The solvent was removed in vacuo to give crude product which was used for the next step without purification. The resulting residue was dissolved in acetonitrile (10 mL) and followed by addition of diethyl amine (6.2 mL, 60 mmol). The mixture was stirred at room temperature for overnight until no starting material was observed by TLC and concentrated in vacuo. The residue was flash chromatographed on silica gel with 5% MeOH/DCM to provide intermediate H (270 mg, yield 54% over two steps). MS (ESI) m/z 162.83 (M+H)+. at room temperature for 1 h until no E was observed by TLC washed with 10% Na2CO3 (100 mL) brine (100 mL) and dried over sodium sulfate The solvent was removed in vacuo to give crude product which was used for the next step without purification The resulting residue was dissolved in acetonitrile (10 mL) The mixture was stirred at room temperature for overnight until no starting material concentrated in vacuo chromatographed on silica gel with 5% MeOH/DCM

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of alcohol E (1.0 g, 3.1 mmol) and methyl sulfide (1.8 mL, 24.8 mmol) in acetonitrile (31 mL) at 0° C. was added benzoyl peroxide (3.0 g, 12.4 mmol) in four equal portions over 10 min, and the mixture was stirred at 0° C. for 1 h and then at room temperature for 1 h until no E was observed by TLC. The mixture was diluted with ethyl acetate (100 mL), washed with 10% Na2CO3 (100 mL) and then brine (100 mL) and dried over sodium sulfate. The solvent was removed in vacuo to give crude product which was used for the next step without purification. The resulting residue was dissolved in acetonitrile (10 mL) and followed by addition of diethyl amine (6.2 mL, 60 mmol). The mixture was stirred at room temperature for overnight until no starting material was observed by TLC and concentrated in vacuo. The residue was flash chromatographed on silica gel with 5% MeOH/DCM to provide intermediate H (270 mg, yield 54% over two steps). MS (ESI) m/z 162.83 (M+H)+. at room temperature for 1 h until no E was observed by TLC washed with 10% Na2CO3 (100 mL) brine (100 mL) and dried over sodium sulfate The solvent was removed in vacuo to give crude product which was used for the next step without purification The resulting residue was dissolved in acetonitrile (10 mL) The mixture was stirred at room temperature for overnight until no starting material concentrated in vacuo chromatographed on silica gel with 5% MeOH/DCM