1-O-tert-butyl 2-O-methyl (2R)-4-oxopyrrolidine-1,2-dicarboxylate

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

Procedure: To slurry of pyridinium dichromate (9.97 g, 26.5 mmol) in dichloromethane (60 mL) at rt was added (2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (5.00 g, 20.39 mmol) in several portions. The resulting mixture was stirred overnight at rt. Celite (5 g) was added and the mixture stirred for 40 min, filtered and the filter cake was rinsed with additional dichloromethane (50 mL×3). The resulting filtrate was concentrated and toluene (40 mL) was added followed by concentration again under vacuum to give ˜6.5 g of a brown syrup as the crude product. Purification by flash silica gel chromatography (120 g column, EtOAc in hexane, 0 to 100% gradiant, 85 mL/min) afforded 4.18 g (84%) of the title compound as a white solid. LCMS (condition A): m/z 144 (M-Boc) −ve. 1H NMR (400 MHz, CDCl3) δ ppm 4.64-4.89 (1 H, m), 3.84-3.96 (2 H, m), 3.77 (3 H, s), 2.81-3.10 (1 H, m), 2.59 (1 H, dd, J=18.93, 1.76 Hz), 1.52 (9 H, s). Celite (5 g) was added the mixture stirred for 40 min filtered the filter cake was rinsed with additional dichloromethane (50 mL×3) The resulting filtrate was concentrated toluene (40 mL) was added followed by concentration again under vacuum

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

Procedure: To slurry of pyridinium dichromate (9.97 g, 26.5 mmol) in dichloromethane (60 mL) at rt was added (2R,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (5.00 g, 20.39 mmol) in several portions. The resulting mixture was stirred overnight at rt. Celite (5 g) was added and the mixture stirred for 40 min, filtered and the filter cake was rinsed with additional dichloromethane (50 mL×3). The resulting filtrate was concentrated and toluene (40 mL) was added followed by concentration again under vacuum to give ˜6.5 g of a brown syrup as the crude product. Purification by flash silica gel chromatography (120 g column, EtOAc in Hexane, 0 to 100% gradiant, 85 mL/min) afforded 4.18 g (84%) of the title compound as a white solid. LCMS (condition A): m/z 144 (M-Boc) −ve. 1H NMR (400 MHz, CDCl3) δ ppm 4.64-4.89 (1 H, m), 3.84-3.96 (2 H, m), 3.77 (3 H, s), 2.81-3.10 (1 H, m), 2.59 (1 H, dd, J=18.93, 1.76 Hz), 1.52 (9 H, s). Celite (5 g) was added the mixture stirred for 40 min filtered the filter cake was rinsed with additional dichloromethane (50 mL×3) The resulting filtrate was concentrated toluene (40 mL) was added followed by concentration again under vacuum