(2-Oxo-pyrrolidin-3-yl)-carbamic acid benzyl ester

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

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

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

Procedure: To a stirred solution of benzyl N-(2-oxopyrrolidin-3-yl)carbamate (which may be prepared as described in Description 39) (0.5 g, 2.13 mmol) in dry DMF (6 mL) was added in 3 equal portions a 60% dispersion of NaH in oil (90 mg, 2.25 mmol) over 5 minutes under N2. After stirring for 55 minutes, 2-(chloromethoxy)ethyl-trimethyl-silane (0.42 mL, 2.35 mmol) was added dropwise over 12 minutes. The solution was stirred under N2 at ambient temp for 19 hours. The reaction was quenched by addition of saturated aqueous NH4Cl solution (2 mL). The mixture was evaporated and re-evaporated from toluene (3×100 mL). The residue was partitioned between DCM (30 mL) and water (30 mL). The organic phase was dried (MgSO4) and evaporated to an oily solid. The material was purified by silica column chromatography: it was dissolved in toluene (6 mL) and the solution was applied to a 50 g cartridge which was then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (30-100%). Relevant fractions were pooled and evaporated to give benzyl N-[2-oxo-1-(2-trimethylsilylethoxymethyl)pyrrolidin-3-yl]carbamate (D40) as a colourless oil, dried under vacuum for 2 hours at room temperature to afford 170 mg; The solution was stirred under N2 at ambient temp for 19 hours The reaction was quenched by addition of saturated aqueous NH4Cl solution (2 mL) The mixture was evaporated re-evaporated from toluene (3×100 mL) The residue was partitioned between DCM (30 mL) and water (30 mL) The organic phase was dried (MgSO4) evaporated to an oily solid The material was purified by silica column chromatography it was dissolved in toluene (6 mL) was then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (30-100%) evaporated

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

Procedure: To a solution of 3-aminopyrrolidin-2-one (2.70 g, 27 mmol) in water (36 mL) at ambient temperature was added triethylamine (4.12 mL, 29.7 mmol, 1.1 equivalent) followed by the dropwise addition over 15 minutes of a solution of N-(benzyloxycarbonyloxy)succinimide (7.4 g, 29.7 mmol, 1.1 equivalent) in MeCN (20 mL). The mixture was stirred at room temperature for 22 hours. The mixture was evaporated and the residue was partitioned between 0.5 M aqueous NaOH (500 mL) and DCM (600 mL). The aqueous fraction was further extracted with DCM (2×250 mL) and the combined organic extracts were back-washed with water (300 mL), dried (MgSO4) and evaporated to a cream solid which was filtered, dried and evaporated then triturated with ether (50 mL) for 0.5 hours, before being dried at room temperature for 2 hours to give benzyl N-(2-oxopyrrolidin-3-yl)carbamate (D39) 4.4 g (70%); The mixture was evaporated the residue was partitioned between 0.5 M aqueous NaOH (500 mL) and DCM (600 mL) The aqueous fraction was further extracted with DCM (2×250 mL) the combined organic extracts were back-washed with water (300 mL) dried (MgSO4) evaporated to a cream solid which was filtered dried evaporated then triturated with ether (50 mL) for 0.5 hours before being dried at room temperature for 2 hours

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