1-O-tert-butyl 2-O-ethyl (2S)-4-hydroxypyrrolidine-1,2-dicarboxylate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice cold solution of 50.0 g (190 mmol) of 6 in 600 mL of tetrahydrofuran was added 15.0 g (690 mmol) of lithium borohydride in one portion. The mixture was stirred at 0° C. for 1 h followed by 15 h at room temperature. The solution was cooled to 0° C. with stirring and 255 mL of water and 100 mL of 1:1 water:concentrated hydrochloric acid were added carefully. The solution was warmed until an organic phase separated. The organic phase was withdrawn and the aqueous layer was extracted with three 150 mL portions of ethyl acetate. The combined organic layers were washed with 100 mL each of 2 N sodium hydroxide, 2 N hydrochloric acid, and brine. The organic layers were dried over magnesium sulfate and evaporated under reduced pressure to an oil. The oil was kept at 0.05 mm for 24 h and then used without further purification. The yield of 7 was 33.9 g (81%). 1H NMR (CDCl3) δ1.1-2.0 (m), 1.48 (s, 9H), 3.3-4.2 (m), 4.4 (s). 13C NMR (CDCl3) δ28.4, 37.2, 54.9, 55.4, 57.7, 58.4, 63.5, 65.9, 68.6, 80.2, 154.8, 156.5; IR (neat) 3400, 1670, 1420 cm-1. followed by 15 h at room temperature The solution was cooled to 0° C. with stirring The solution was warmed until an organic phase separated The organic phase was withdrawn the aqueous layer was extracted with three 150 mL portions of ethyl acetate The combined organic layers were washed with 100 mL each of 2 N sodium hydroxide, 2 N hydrochloric acid, and brine The organic layers were dried over magnesium sulfate evaporated under reduced pressure to an oil The oil was kept at 0.05 mm for 24 h used without further purification

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 100 g (510 mmol) of 5, 75.0 mL (540 mmol) of t-butoxycarbonylazide, 150 mL of triethylamine, 500 mL of water and 500 mL of p-dioxane was heated under nitrogen to 50° C. for 15 h. The mixture was reduced in volume by one half on a rotary evaporator and extracted with four 100 mL portions of ether. The combined extracts were washed with brine, dried over magnesium sulfate and concentrated to a yellow oil under reduced pressure. Distillation of the oil under reduced pressure gave 97.5 g (69.6%) of 6 was a pale yellow oil: bp 126°-128° C. (0.05 mm); 1H NMR (CDCl3) δ1.27 (t, 3H, J=7 Hz), 1.45 (s, 9H), 1.8-2.4 (m), 3.4-3.7 (m), 4.2 (q, 2H, J=7 Hz), 4.4-4.6 (m); 13CNMR (CDCl3) δ14.2, 28.2, 28.3, 38.2, 39.0, 54.4, 57.7, 58.0, 60.9, 68.7, 69.4, 79.9, 80.1, 153.8, 154.3, 172.7, 173.0; IR (neat) 3450, 1735, 1680 cm-1. [α]D20 -68.3° C. (c=2, EtOH) (lit. [α]D20 -67.8° C. (c=1.75, EtOH). The mixture was reduced in volume by one half on a rotary evaporator extracted with four 100 mL portions of ether The combined extracts were washed with brine dried over magnesium sulfate concentrated to a yellow oil under reduced pressure Distillation of the oil under reduced pressure