[N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)([O-])=O.[CH:13]1[CH:18]=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=C[CH:14]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=[O:35].[Li+].[OH-].Cl>CCOC(C)=O.C1COCC1.O>[OH:35][C@H:5]1[C:6]2=[N:1][CH:4]=[CH:12][CH:11]=[C:7]2[C:8](=[O:10])[CH2:18][CH2:13][CH2:14]1In a 1 L round-bottomed flask was (S)-9-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-one (19.14 g, 108 mmol) (obtained by enzyme reduction of the diketone) in THF (300 mL) to give a light orange solution. 4-Nitrobenzoic acid (27.1 g, 162 mmol) and Ph3P (42.5 g, 162 mmol) were added under nitrogen, and the mixture was cooled to 0° C. Diisopropyl azodicarboxylate (31.9 mL, 162 mmol) was added dropwise. The mixture was allowed to gradually warm to rt and stirred overnight (5:00 pm). The color changed to tan. 15 h: LCMS showed complete conversion. 80 ml water was added followed by LiOH (7.76 g, 324 mmol). The mixture was stirred at rt for 2 h (some LiOH was not completely dissolved). 2 h: LCMS showed complete conversion (product/dehydrated ˜7/1 by intergration). THF was stripped off and the remaining mixture was slowly acidified with 40 ml concentrated HCl (12N). 300 ml EtOAc was added. The mixture was shaken in a 1L separating funnel. (10 ml hexane was added for better separation). The layers were separated and the organic layer was extracted with water (2×50 mL). The combined aqueous layers were washed with EtOAc (4×100 mL). The tan aqueous solution was then basified slowly with 50 mL ION NaOH and was extracted with EtOAc (4×150 mL). The aqueous layer was saturated with NaCl and extracted with EtOAc (2×100 mL). The combined tan organic layers (TLC showed desired product, dehydrated product and some baseline) were washed with brine, dried and concentrated to a tan oil (crude weight: 19.24 g, 100%), which was directly used in the next step. MS(ESI)[M+H+]=178.24.
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