tert-butyl (2R)-2-carbamoylpyrrolidine-1-carboxylate

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

Procedure: The title product of Example 10 (10.81 g, 50.45 mmol) and cyanuric chloride (5.58 g, 30.3 mmol) was stirred in DMF (30 mL) for 1 h. The reaction mixture was partitioned between ethyl acetate and water. The organic extracts were washed with aq. sodium carbonate, water, brine dried over sodium sulphate, filtered and concentrated to afford the title product (8.34 g, 84%) as a colourless oil. The reaction mixture was partitioned between ethyl acetate and water The organic extracts were washed with aq. sodium carbonate, water, brine dried over sodium sulphate filtered concentrated

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

Procedure: N-Methylmorpholine (9.85 g, 97.5 mmol) and isobutyl chloroformate (13.33 g, 97.5 mmol) was added to (R)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (20.0 g, 92.9 mmol) in THF (200 mL) at −78° C. and stirred for 1 h. Ammonium hydroxide (58 mL) was added slowly as the reaction warmed up to RT and stirred for a further 2 h. The reaction mixture was partitioned between DCM and water. The organic extracts were washed with 1 M HCl, dried over sodium sulphate, filtered and concentrated to afford the title product (10.8 g, 54%) as a colourless semisolid. stirred for a further 2 h The reaction mixture was partitioned between DCM and water The organic extracts were washed with 1 M HCl dried over sodium sulphate filtered concentrated

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

Procedure: N-Methylmorpholine (9.85 g, 97.5 mmol) and isobutyl chloroformate (13.33 g, 97.5 mmol) was added to (R)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (20.0 g, 92.9 mmol) in THF (200 mL) at −78° C. and stirred for 1 h. Ammonium hydroxide (58 mL) was added slowly as the reaction warmed up to RT and stirred for a further 2 h. The reaction mixture was partitioned between DCM and water. The organic extracts were washed with 1 M HCl, dried over sodium sulphate, filtered and concentrated to afford the title product (10.8 g, 54%) as a colourless semisolid. stirred for a further 2 h The reaction mixture was partitioned between DCM and water The organic extracts were washed with 1 M HCl dried over sodium sulphate filtered concentrated

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

Procedure: To a stirred solution Boc-D-prolinamide (2.63 g, 12.3 mmol) in CH2Cl2 (25 mL) at rt was added Lawesson's reagent (2.73 g, 6.75 mmol). The mixture was stirred overnight and concentrated. The oily residue was purified by chromatography on a 40-g silica gel cartridge, eluted with a 0-20% MeOH in CH2Cl2 gradient, to afford (R)-tert-butyl 2-carbamothioylpyrrolidine-1-carboxylate (2.65 g, 94%) as a tan solid. LC-MS Method 1 tR=1.23 min, m/z=231, 173, 131. concentrated The oily residue was purified by chromatography on a 40-g silica gel cartridge eluted with a 0-20% MeOH in CH2Cl2 gradient