benzyl 2,5-dihydropyrrole-1-carboxylate

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

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

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

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

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

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 solution of 2,5-dihydro-1H-pyrrole (30 g, 434 mmol) in dioxane (0.43 M solution) was added CbzOSu (130 g, 521 mmol). After being stirred at room temperature for 18 h, the reaction mixture was concentrated to around 300 mL, diluted with 1000 mL of EtOAc. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The desired benzyl 2,5-dihydro-1H-pyrrole-1-carboxylate was obtained in 91% yield (80.0 g) as a colorless oil by flash column chromatography. 1H NMR (CDCl3, 400 MHz): δ 7.32 (5H, m), 5.80 (2H, m), 5.77 (2H, s), 4.22 (4H, m). LC/MS (uplc): MH+ 204.2, 160.1 (−44), 0.86 min. the reaction mixture was concentrated to around 300 mL diluted with 1000 mL of EtOAc The organic layer was washed with water and brine dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

Procedure: 43 mL benzyloxycarbonyl chloride in 135 mL dichlormethane was added to 17.6 g 1-benzyl-2,5-dihydro-1H-pyrrole in 135 mL dichlormethane at 0° C. in 60 min. The mixture was stirred 3 h at RT and washed with saturated sodium hydrogencarbonate solution. The organic layer was dried and evaporated. The residue was purified by chromatography on silica gel (hexane/ethyl acetate: 5/1) to give 19.7 g of the desired product. washed with saturated sodium hydrogencarbonate solution The organic layer was dried evaporated The residue was purified by chromatography on silica gel (hexane/ethyl acetate: 5/1)

Conditions: temp:46.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzyl 2,5-dihydro-1H-pyrrole-1-carboxylate (11.0 g, 54.1 mmol, commercially available from Aldrich) and 3-chlorobenzoperoxoic acid (17.3 g, 70.4 mmol) were added to 150 mL of chloroform and heated to 46° C. for 20 hours. The mixture was cooled, dichloromethane was added, and the reaction was washed with a saturated solution of NaHCO3 and Na2S2CO3. The combined organic layers were dried over MgSO4, filtered and concentrated to give 10.5 g (88% isolated yield) of the desired compound as an oil, which was used directly in the next step. The mixture was cooled the reaction was washed with a saturated solution of NaHCO3 and Na2S2CO3 The combined organic layers were dried over MgSO4 filtered concentrated to give

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

Procedure: To a solution of 2,5-dihydro-1H-pyrrole (30 g, 434 mmol, 96% from Alfa Aesar) in dioxane (1000 mL, 0.43 M solution) was added CbzOSu (130 g, 521 mmol). After being stirred at room temperature for 18 h, the reaction mixture was concentrated to around 300 mL, diluted with 1000 mL of EtOAc. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The desired benzyl 2,5-dihydro-1H-pyrrole-1-carboxylate was obtained in 91% yield (80.0 g) as a colorless oil by flash column chromatography. Rf==0.6 (30% EtOAc in hexanes). 1H NMR (CDCl3, 400 MHz): δ 7.32 (5H, m), 5.80 (2H, m), 5.77 (2H, s), 4.22 (4H, m). LC/MS (uplc): MH+ 204.2, 160.1 (−44), 0.86 min. the reaction mixture was concentrated to around 300 mL diluted with 1000 mL of EtOAc The organic layer was washed with water and brine dried over anhydrous Na2SO4 filtered concentrated in vacuo

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

Procedure: To a solution of 30 g (133 mmol) of benzyl 3-pyrroline-1-carboxylate in 700 mL of methylene chloride was added 57.2 g (200 mmol) of mCPBA. The reaction mixture was stirred at room temperature overnight and quenched with 250 mL of 20% NaHSO3 aqueous solution. The organic phase was separated, and the aqueous layer was extracted with methylene chloride twice (100 mL×2). The combined extracts were washed with saturated NaHCO3 aqueous solution twice (250 mL×2), brine, dried over Na2SO4, evaporated under reduced pressure. Chromatography on silica gel column with 40% EtOAc-Hexane provided the title compound (24 g, 83%). MS (M+H)+ 220. quenched with 250 mL of 20% NaHSO3 aqueous solution The organic phase was separated the aqueous layer was extracted with methylene chloride twice (100 mL×2) The combined extracts were washed with saturated NaHCO3 aqueous solution twice (250 mL×2), brine dried over Na2SO4 evaporated under reduced pressure