[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:36](O)(=[O:38])[CH3:37].N(C(OCC)=O)=NC(OCC)=O>C1(C)C=CC=CC=1>[C:36]([O:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:3]1)(=[O:38])[CH3:37]A 22-L, 3 neck round bottom flask equipped with a mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 422 g (1.91 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate (Intermediate 1, Step A), 12 L of toluene, 751 g (2.86 mol) of triphenylphosphine, and 164 mL (2.86 mol) of glacial acetic acid. The resultant mixture was stirred at ambient temperature and then 500 g (2.87 mol) of diethyl azodicarboxylate was added via the addition funnel over a period of about 30 min, keeping the internal temperature below 28° C. with a cold water bath. The reaction was stirred at ambient temperature overnight. The solvent was removed in vacuo and the residue was triturated with 6 L of diethyl ether. The solid was filtered off and washed well with diethyl ether. The filtrate and ether washings were combined and concentrated to a thick yellow oil with solids. Purification by flash chromatography (silica gel, eluting sequentially with 5% and a gradient of 10% to 30% ethyl acetate/hexane) gave the title compound as a pale yellow oil.
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