2-Methoxy-5-nitrobenzaldehyde

2-Hydroxy-5-nitrobenzaldehyde (1) (2 g, 12.0 mmol) was methylated using methyl iodide (1.7 g, 36 mmol) and anhydrous potassium carbonate (1.7 g, 36 mmol) in DMF (7 mL), by stirring at room temperature for 12 h. After the TLC showed complete disappearance of the starting material, the reaction mixture was poured in to crushed ice leading to the precipitation of the product. This was further purified by column chromatography over silica gel using 1:10 ethyl acetate/hexane to obtain a yield of 94percent (2.04 g) of compound (2). For characterization, the spectroscopic data was consistent with what has been previously reported (Yang et al., 2007, Org. Lett. 9:5287).Synthesis of 5-(N-methyl-N-methylsulfonylamino)-o-anisaldehyde A solution of Intermediate 312A (520 mg, 2.92 mmol) in Et20 (23.400 mL) was cooled to 0 °C under an atmosphere of N2. A solution of DIBA1-H (1.0 M in Toluene) (4.38 mL, 4.38 mmol) was then added dropwise causing bubbling to occur. After 5 mmstirring, the reaction mixture was allowed to thaw to room temperature. After an additional 3 h, the orange solution was poured into a mixture of ice and 10 mL of glacialacetic acid. This mixture was stirred while the ice melted, diluted with EtOAc and DIwater and then extracted. The organic phase was concentrated and purified by ISCO(80g, 0-100percent EtOAc/Hexanes, 28 mm. Product at 55percent) to afford Intermediate 3 12B(410 mg, 1.811 mmol, 62.0 percent yield) as a light orange solid. LC-MS. Method H, RT =0.77 mm, MS (ESI) m/z: 182.1 (M+H). ‘HNMR (400MHz, CHLOROFORM-d)10.46 (s, 1H), 8.71 (d, J=2.9 Hz, 1H), 8.45 (dd, J=9.2, 2.9 Hz, 1H), 7.12 (d, J=9.2 Hz, 1H), 4.08 (s, 3H).2, 4-Pentadione (1.0 g, 0.01 mol) was added to a solution of 2-Hydroxy-5-nitrobenzaldehyde (1) (2 g, 12.0 mmol) was methylated using methyl iodide (1.7 g, 36 mmol) and anhydrous potassium carbonate (1.7 g, 36 mmol) in DMF (7 mL), by stirring at room temperature for 12 h. After the TLC showed complete disappearance of the starting material, the reaction mixture was poured in to crushed ice leading to the precipitation of the product. This was further purified by column chromatography over silica gel using 1:10 ethyl acetate/hexane to obtain a yield of 94% (2.04 g) of compound (2). For characterization, the spectroscopic data was consistent with what has been previously reported (Yang et al., 2007, Org. Lett. 9:5287).1H NMR (CDCl3, 500 MHz): delta 10.48 (1H, s), 8.7 (1H, d, J=3.0 Hz), 8.47 (1H, dd, J=9 Hz), 7.05 (1H, d, 9 Hz), 4.04 (3H, s); 13C NMR (CDCl3, 100 MHz): 187.8, 165.8, 141.8, 130.9, 124.8, 112.5, 57.0.Synthesis of 5-(N-methyl-N-methylsulfonylamino)-o-anisaldehyde To a solution of 5-nitrosalicylaldehyde (1.00 g, 6.0 mmol) in DMF (20 ml) was added NaH (246 mg) and methyl iodide (2.56 g, 18 mmol) at 0 C. The mixture was stirred for 8.5 hr at 60 C. After the reaction mixture was extracted with ether, the extract was washed with aqueous NaHCO3, brine and 5%-HCl/aq.NaCl, dried over MgSO4 and concentrated in vacuo to afford Into a 20 L round-bottom flask was charged 2-hydroxy-5-nitrobenzaldehyde (1.6 kg, 1.0 eq) and DMF (8.0 L, 5.0 v/w). K2CO3 (2.6 kg, 2.0 eq.) was added into the mixture followed by the dropwise addition of CH3I (1.5 kg, 1.1 eq.) at 15~35C.The reaction was heated to 40-50C. The reaction was monitored by HPLC until 2-hydroxy-5-nitrobenzaldehyde was present in less than 5.0%. Water (16 L, 10 v/w) was added into the mixture. The reaction was stirred for 12 hours at 20±5C. The reaction was filtered and the filter cake was washed with water (3.2 L, 2.0 v/w) twice. The filter cake was col lected and dried under vacuum at 40-50C. This resulted in an off-white product (1.52 kg, purity: 99.7%, yield: 87.4%).

Molecular Weight:181.15
XLogP3:1.6
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:181.03750770
Monoisotopic Mass:181.03750770
Topological Polar Surface Area:72.1
Heavy Atom Count:13
Complexity:201
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes