[OH:1][CH2:2][CH:3]1[CH2:20][N:7]2[CH2:8][CH2:9][N:10]([C:12]3[C:17]([Cl:18])=[CH:16][C:15]([Cl:19])=[CH:14][N:13]=3)[CH2:11][CH:6]2[CH2:5][CH2:4]1.[F:21][C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.Cl>C1COCC1.C(OCC)(=O)C.CCOCC>[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:1][CH2:2][CH:3]2[CH2:20][N:7]3[CH2:8][CH2:9][N:10]([C:12]4[C:17]([Cl:18])=[CH:16][C:15]([Cl:19])=[CH:14][N:13]=4)[CH2:11][CH:6]3[CH2:5][CH2:4]2)=[CH:24][CH:23]=1A solution of 0.50 g (1.58 mmol) of (7RS,9aSR)-7-hydroxymethyl-2-(3,5-dichloro-pyridin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine in 40 mL of THF with 0.266 g (2.32 mmol) of 4-fluorophenol, 0.498 g (1.90 mmol) of triphenylphosphine, and 0.30 mL (1.90 mmol) of diethyl azodicarboxylate was stirred at room temperature for 16 h. The mixture was diluted with ethyl acetate and treated with excess HCl(g) in ether. The solvent was evaporated and the residue washed repeatedly with 1:1 ethyl acetate:ether. The white powder was dissolved in chloroform, washed with 1M NaOH (2×), dried (magnesium sulfate), filtered and evaporated. The crude product was purified by flash silica gel chromatography with 50:50 ethyl acetate: hexane to give 0.566 g (87%) of title compound. mp (.HCl) 247–248° C. 13C NMR (base, CDCl3): δ 27.1, 29.0, 36.4, 49.0, 54.4, 54.8, 58.6, 60.7, 71.7, 115.36, 115.47, 115.59, 115.89, 122.3, 124.0, 138.2, 155.1, 155.6, 156.6, 158.8. HRMS calc for C20H22Cl2FN3O: 409.1124, found: 409.1141.
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