benzyl (2S)-2-methylpiperazine-1-carboxylate

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

Procedure: A mixture of 4-bromobenzaldehyde (1.19 g, 6.42 mmol), phenylmethyl (2S)-2-methyl-1-piperazinecarboxylate (1.505 g, 6.42 mmol) and sodium triacetoxyborohydride (2.04 g, 9.63 mmol) in 1,2-DCE (15 ml) was stirred at room temperature overnight. Saturated aq. NaHCO3 solution was added and the mixture stirred for 30 mins. Product was extracted and the extracts dried (Na2SO4). Chromatography (0-30% EtOAc in pentane) gave the title compound (2.18 g). MS (ES): MH+ 403/405. the mixture stirred for 30 mins Product was extracted the extracts dried (Na2SO4)

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

Procedure: A mixture of 4-bromobenzaldehyde (1.19 g, 6.42 mmol), phenylmethyl (2S)-2-methyl-1-piperazinecarboxylate (1.505 g, 6.42 mmol) and sodium triacetoxyborohydride (2.04 g, 9.63 mmol) in 1,2-DCE (15 ml) was stirred at room temperature overnight. Saturated aq. NaHCO3 solution was added and the mixture stirred for 30 mins. Product was extracted and the extracts dried (Na2SO4). Chromatography (0-30% EtOAc in pentane) gave the title compound (2.18 g). MS (ES): MH+ 403/405. the mixture stirred for 30 mins Product was extracted the extracts dried (Na2SO4)

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

Procedure: A mixture of 4-bromobenzaldehyde (1.19 g, 6.42 mmol), phenylmethyl (2S)-2-methyl-1-piperazinecarboxylate (1.505 g, 6.42 mmol) and sodium triacetoxyborohydride (2.04 g, 9.63 mmol) in 1,2-DCE (15 ml) was stirred at room temperature overnight. Saturated aq. NaHCO3 solution was added and the mixture stirred for 30 mins. Product was extracted and the extracts dried (Na2SO4). Chromatography (0-30% EtOAc in pentane) gave the title compound (2.18 g). MS (ES): MH+ 403/405. the mixture stirred for 30 mins Product was extracted the extracts dried (Na2SO4)

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

Procedure: To a solution of 3.0 g (S)-2-Methyl-piperazine-1-carboxylic acid benzyl ester hydrotrifluoroacetate in 17 ml dichloromethane were added at 0° C. 7.1 ml triethylamine and 1.2 ml ethyl chloroformate. After 12 h the reaction mixture was diluted with dichloromethane and extracted with 0.1 M HCl and saturated aqueous NaHCO3. The organic layer was dried over MgSO4 and the crude product obtained after evaporation purified by chromatography on silica using heptane/ethyl acetate 2/1 as eluent. Yield: 3.5 g. extracted with 0.1 M HCl and saturated aqueous NaHCO3 The organic layer was dried over MgSO4

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

Procedure: A solution of 4.3 g (S)-2-Methyl-piperazine-1,4-dicarboxylic acid 1-benzyl ester 4-tert-butyl ester in 20 ml dichloromethane was stirred in the presence of 10 ml TFA for 16 h. The solution was concentrated and the residue codistilled twice with toluene to give the crude hydrotrifluoroacetate. Yield: 6.4 g. The solution was concentrated to give the crude hydrotrifluoroacetate

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

Procedure: A solution of phenylmethyl (2S)-2-methyl-1-piperazinecarboxylate (commercially available) (1 g, 4.3 mmol) and benzyloxyacetaldehyde (0.9 mL, 6.4 mmol) in DCM (50 mL) was stirred for 30 minutes, and then NaBH(OAc)3 (1.36 g, 6.4 mmol) was added. The reaction was stirred overnight before being quenched with 1 M NaOH. The phases were separated and the aqueous layer was extracted with DCM. The combined organics were washed with brine, dried over sodium sulfate and concentrated to a crude residue, which was purified by silica gel chromatography (5-95% EtOAc in hexane) yielding phenylmethyl (2S)-2-methyl-4-{2-[(phenylmethyl)oxy]ethyl}-1-piperazinecarboxylate (0.93 g, 58%). LCMS: (M+H)+: 369.1 before being quenched with 1 M NaOH The phases were separated the aqueous layer was extracted with DCM The combined organics were washed with brine dried over sodium sulfate concentrated to a crude residue, which was purified by silica gel chromatography (5-95% EtOAc in hexane)