O.[PH2]([O-])=O.[Na+].[CH2:6]([O:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#N)=[C:16]([NH:22][CH2:23][C@H:24]([OH:26])[CH3:25])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.N1C=CC=CC=1CC(O)=[O:35].O>[Ni]>[CH2:6]([O:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=[O:35])=[C:16]([NH:22][CH2:23][C@H:24]([OH:26])[CH3:25])[CH:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1Sodium hypophosphite hydrate (986 g, 11.2 mol) and Raney nickel (500 g of a 50% aqueous suspension) were added to a solution of the product from Step B (790 g, 2.8 mol) in a 2:1:1 mixture of pyridine-acetic acid-water (7 L). The mixture was stirred at 45° C. for 7 h, then cooled to 25° C. overnight and filtered through a filter-aide rinsing with water and ethyl acetate. The filtrate was washed with saturated sodium hydrogenphosphate to pH 5, water and brine, dried over sodium sulfate and concentrated. During concentration, 4 L of heptane was added to azeotropically remove pyridine. After 8 L of solvent had been removed the product solidified. Heptane (5 L) was added and the solid was triturated, isolated by filtration and vacuum dried at 35° C. to yield the desired product (722 g, 90%).
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