[H-].[Na+].[CH2:3]([O:5][C:6](=[O:31])[CH:7](P(OCC)(OCC)=O)[CH2:8][C:9]1[CH:10]=[N:11][C:12]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:13][CH:14]=1)[CH3:4].C(=O)C.[CH2:35]1[CH2:39]O[CH2:37][CH2:36]1>>[CH2:3]([O:5][C:6](=[O:31])[C:7]([CH2:8][C:9]1[CH:10]=[N:11][C:12]([NH:15][C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])=[CH:13][CH:14]=1)=[C:35]([CH2:36][CH3:37])[CH3:39])[CH3:4]To a suspension of NaH (278.8 mg, 60% in mineral oil, 6.97 mmol) in THF (25 mL) at 0° C. was added a solution of 3-(6-tert-butoxycarbonylamino-pyridin-3-yl)-2-(diethoxyphosphoryl)-propionic acid ethyl ester (2.5 g, 5.81 mmol) in THF (30 mL). The reaction mixture was allowed to stir at 0° C. for 1 h. To the reaction was added acetaldehyde (512 mg, 11.6 mmol) dropwise at 0° C. The reaction mixture was allowed to warm to room temperature and then stir for 16 h. Acetaldehyde (2.0 g) was added to the reaction vessel and the reaction mixture was allowed to stir at room temperature for an additional 16 h. The reaction was quenched with the slow addition of saturated aqueous ammonium chloride (30 mL). The mixture was extracted with EtOAc, washed with brine and dried to afford the crude product. The crude product was purified by column chromatography (EtOAc/hexane, 1:8) to give ethyl 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-but-2-enoic acid ethyl ester as a mixture of isomers (1.1 g, 60%).
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