C[C:2]1([CH3:10])[O:7][C:6](=[O:8])[CH2:5][C:4](=[O:9])O1.C(Cl)Cl.N1C=CC=CC=1.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27](C)[C:28](Cl)=O)=[CH:23][CH:22]=1.Cl.C(O)C>>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]([CH3:28])[C:4](=[O:9])[CH2:5][C:6]([O:7][CH2:2][CH3:10])=[O:8])=[CH:23][CH:22]=1In a round bottomed flask, to a suspension of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid, 2.91 g, 20.2 mmol) in methylene chloride (11.3 mL, 177 mmol) at −10° C. (internal temp) was added pyridine (4.00 mL, 49.5 mmol) over 10 minutes. To the resulting clear solution at −10° C., was added dropwise a solution of 2-(4-chlorophenyl)propanoyl chloride (4.10 g, 20.2 mmol) in methylene chloride (7.93 mL, 124 mmol) over 1 h. The reaction mixture was then stirred for 1 h at −10° C., and then for 1 hour at room temperature. The mixture was poured into hydrochloric acid (2.00M in water, 45.3 mL, 90.6 mmol) and ice, the layers were separated, and the aqueous phase was extracted with CH2Cl2. The combined organic layers were washed with 1N HCl and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. To the crude residue was added ethanol (39.6 mL, 679 mmol) and the mixture was heated at reflux (89 degree bath temp) for 3 hours. After cooling to room temp, the volatiles were removed in vacuo. Residue was adsorbed onto silica using DCM and purified via column chromatography (gradient elution: 0 to 20% EtOAc/hexanes to afford ethyl 4-(4-chlorophenyl)-3-oxopentanoate (2.94 g, 92%) as a yellow oil. LCMS: (FA) ES+ 255; 1H NMR (400 MHz, DMSO) δ 7.34-7.30 (m, 2H), 7.17-7.13 (m, 2H), 4.16-4.09 (m, 2H), 3.90 (q, J=7.2, 1H), 3.40 (d, J=15.6, 1H), 3.30 (d, J=15.6, 1H), 1.40 (d, J=6.8, 3H), 1.23 (t, J=7.2, 3H).
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