4-Chloro-3-methoxybenzaldehyde

To a solution of (4-chloro-3-methoxyphenyl)methan-1-ol (5.08 g, 29.4 mmol) in benzene (120 mL) was added MnO[00154] Step 2. A suspension of pyridinium chlorochromate (1.37 g, 6.34 mmol) in dichloromethane (35 mL) was treated with Celite (2.0 g) and stirred at rt. A solution of (4-chloro-3-methoxyphenyl)methanol (730 mg, 4.23 mmol) in dichloromethane (5 mL) was added in one portion, and the resulting mixture was stirred at rt for 3 h. After this time, the mixture was diluted with diethyl ether, and stirred vigorously. The mixture was then filtered through a pad of silica gel and the collected solids were rinsed with additional diethyl ether. The combined filtrates were concentrated under vacuum to provide 4-chloro-3-methoxybenzaldehyde as a pale tan-yellow solid (630 mg, 87percent). Step 2;. 4-Chloro-3- (methyloxy) benzaldehyde; Ceric ammonium nitrate (43.3 g, 79.0 mmol, 4.00 equiv) was dissolved in 1: 1 HOAc/H2O (200 mL). This solution was added dropwise over one hour to a stirred solution of the product from Step 1 (3.09g, 19 7 mmol, 1.00 equiv) in 1: 1 HOAc/H2O (100 mL) at 100 °C. After the addition was complete, the reaction was stirred for an additional 15 minutes. The reaction was cooled, diluted with H20 and extracted twice with Et20. The combined organic extracts were washed three times with H20, three times with satd. NaHC03, and once with brine. The organic phase was dried over MgS04 and concentrated en vacuo to afford the title compound (3. 00g, 89percent) as an amber oil. 1H NMR (400 MHz, CDCL3) 9.97 (s, 1H), 7. 57 (d, 1H), 7.46 (s, 1H), 7.43 (d, 1H), 4.00 (s, 3H).4-Chloro-3-methoxybenzaldehyde bis-(2, 2, 2-trifluoroethyl)acetal (2); NaH (60percent in mineral oil, 8.06 g, 0.2 mole) was washed 3 times (3.x.30 ml) with hexanes under an argon atmosphere. Two equivalents of 2, 2, 2-trifluoroethanol (13 ml, 0.18 mole) were slowly added at 0° C., generating hydrogen gas immediately as observed from an attached gas bubbler. The suspended mixture became viscous and the magnetic stirring bar was unable to spin at the end of addition. After the first addition of 13 ml 2, 2, 2-trifluoroethanol, an additional 2, 2, 2-trifluroethanol (87 ml) was carefully poured into the reaction vessel down the vessel walls; violent evolution of hydrogen gas occurred several times. Finally, the reaction stirred freely and a milky suspension resulted. 1-Chloro-4-dichloromethyl-2-methoxy-benzene 1 (20.2 g, 89.5 mmole) was added rapidly to the above sodium 2, 2, 2-trifluoroethoxide suspension through a syringe at 0° C. 2, 2, 2-Trifluoroethanol (26 ml) was used to rinse the syringe and added to the mixture. Vacuum-dried silver carbonate (49.9 g, 179 mmole) was then added in one portion to the solution. Following immediate removal of the ice bath, the suspended mixture was stirred at room temperature for 5 minutes, then heated at 8085° C. (bath temperature) for 90 minutes. The mixture became viscous again during the reaction. More 2, 2, 2-trifluoroethanol (54 ml) was added to keep the reaction stirring smoothly. The mixture was cooled and diluted with EtOAc. Some solid was filtered off and rinsed with EtOAc, combining the rinses with the filtrate. After concentration of filtrate, a cloudy oil was obtained. The crude product was partitioned between saturated NaHCOTo a solution of Step 1: Preparation of l-ehloro-2-methox -4-|2-nitroprop-l-enyl| benzene To a solution of