[CH3:1][O:2][CH:3]([O:18][CH3:19])/[CH:4]=[C:5](/S(C1C=CC=CC=1)=O)\[C:6]([O:8][CH3:9])=[O:7].[OH:20]/[N:21]=[C:22](\Cl)/[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CCN(CC)CC.CCCCCC>C(Cl)Cl>[CH3:1][O:2][CH:3]([O:18][CH3:19])[C:4]1[C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[N:21][O:20][C:5]=1[C:6]([O:8][CH3:9])=[O:7]
To a solution of (E)-methyl 4,4-dimethoxy-2-(phenylsulfinyl)but-2-enoate (0.284 g, 1 mmol) and (Z)-N-hydroxybenzimidoyl chloride (0.370 g, 2.378 mmol) in DCM (5 mL) at rt was added Et3N (0.488 mL, 3.50 mmol) dropwise over 30 minutes as a solution in 5 mL of DCM. After stirring 18 hr at rt, the reaction mixture was cooled to 0° C. and additional (Z)-N-hydroxybenzimidoyl chloride (0.370 g, 2.378 mmol) was added. The cooling bath was removed and the reaction mixture stirred for 2 hr during which the temperature of the reaction reached rt, Et3N (0.488 mL, 3.50 mmol) was added over ˜2 minutes. The reaction mixture was stirred an additional 18 hr at rt. The reaction mixture was poured into ˜100 ml of hexane. The resulting suspension was allowed to stand at rt for 30 minutes. After filtration, the filtrate was concentrated and the residue was chromatographed on a 5×12 cm silica gel column, eluting with a 0-6% EtOAc/Hex gradient. (Note: to load the column, the residue was slurried in 5% CH2Cl2/Hex. Not all of the material dissolved). The essentially pure fractions containing the product were concentrated to afford methyl 4-(dimethoxymethyl)-3-phenylisoxazole-5-carboxylate (125 mg, 0.451 mmol, 45.1% yield) as a colorless oil. (Note: The desired product is the third product to elute and began eluting at 6% EtOAc/Hex.). HPLC retention time=1.63 minutes (PHENOMENEX® Luna 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1% TFA over a 2 minute gradient. MS: (M+H)=278.12. 1H NMR (400 MHz, chloroform-d) δ ppm 3.41 (s, 6H), 4.03 (s, 3H), 5.95 (s, 1H), 7.45 (m, 3H), 7.96 (dd, J=7.8, 2.0 Hz, 2H).
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