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

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

Procedure: The title compound of Example 11 (8.34 g, 42.5 mmol), sodium azide (3.04 g, 46.8 mmol), and ammonium chloride (2.50 g, 46.8 mmol) were stirred in DMF (30 mL) at 100° C. for 12 h. The reaction was concentrate and partitioned with DCM and 3 M HCl. The organic extracts were dried over sodium sulphate, filtered and concentrated. The resulting solid was triturated with ether and filtered to afford the title product (5.31 g, 52%) as a white solid. The reaction was concentrate partitioned with DCM and 3 M HCl The organic extracts were dried over sodium sulphate filtered concentrated The resulting solid was triturated with ether filtered

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

Procedure: The title compound of Example 11 (8.34 g, 42.5 mmol), sodium azide (3.04 g, 46.8 mmol), and ammonium chloride (2.50 g, 46.8 mmol) were stirred in DMF (30 mL) at 100° C. for 12 h. The reaction was concentrate and partitioned with DCM and 3 M HCl. The organic extracts were dried over sodium sulphate, filtered and concentrated. The resulting solid was triturated with ether and filtered to afford the title product (5.31 g, 52%) as a white solid. The reaction was concentrate partitioned with DCM and 3 M HCl The organic extracts were dried over sodium sulphate filtered concentrated The resulting solid was triturated with ether filtered

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

Procedure: The title compound of Example 11 (8.34 g, 42.5 mmol), sodium azide (3.04 g, 46.8 mmol), and ammonium chloride (2.50 g, 46.8 mmol) were stirred in DMF (30 mL) at 100° C. for 12 h. The reaction was concentrate and partitioned with DCM and 3 M HCl. The organic extracts were dried over sodium sulphate, filtered and concentrated. The resulting solid was triturated with ether and filtered to afford the title product (5.31 g, 52%) as a white solid. The reaction was concentrate partitioned with DCM and 3 M HCl The organic extracts were dried over sodium sulphate filtered concentrated The resulting solid was triturated with ether filtered

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: General procedure D was used to deprotect 1.4 mmols of 41 using 14 mL of dichloromethane and trifluoroacetic acid. After previously described recrystallization techniques, the TFA salt of 41 was coupled to 0.4 grams (1.4 mmols) of 4-dodecylbenzoic acid using 0.73 grams (1.4 mmols) of PyBOP and 0.72 grams (5.6 mmols) of N,N-diisopropylethylamine in 14 mL of dichloromethane according to general procedure E. Using previously described work-up and purification techniques (column chromatography, 25% EtOAc in hexanes), yielded 0.2 grams (0.55 mmols, 39%) of the title product as an off-white solid. 1H and 13C NMR data were identical to that of 29. After previously described recrystallization techniques work-up and purification techniques (column chromatography, 25% EtOAc in hexanes)

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2 grams (9.3 mmols) of N-Boc-D-Proline in 19 mL of dichloromethane was added 4.2 grams (42 mmols) of triethylamine. The reaction mixture was cooled to −25° C. and 2.5 grams (18.6 mmols) of iso-butylchloroformate was added dropwise. After stirring at this low temperature for 45 minutes, 0.83 grams (49 mmols) of ammonia was added to the mixture as a 7M solution in methanol. The reaction vessel was warmed slowly to ambient temperature and the solution was stirred for an additional 16 hours. After this time, the reaction mixture was evaporated to dryness and reconstituted in 200 mL of EtOAc. The organic layer was washed with four 15 mL portions of 1N HCl, dried with MgSO4 and evaporated to dryness. The crude material was immediately subjected to general procedure E using 2 grams (18.9 mmols) of triethylamine and 2.3 grams (11.16 mmols) of trifluoroacetic anhydride in 93 mL of THF. After previously described purification procedures (column chromatography, 25% EtOAc in hexanes), 0.8 grams (4.1 mmols, 44%) of the title product was recovered. 1H and 13C NMR data were identical to that reported for 28. The reaction vessel was warmed slowly to ambient temperature the solution was stirred for an additional 16 hours After this time, the reaction mixture was evaporated to dryness The organic layer was washed with four 15 mL portions of 1N HCl dried with MgSO4 evaporated to dryness