5-Methoxy-2-nitrobenzaldehyde

Step 1. 5-Hydroxy-2-nitrobenzaldehyde (25.0 g, 150 mmol) was dissolved in N, N- dimethylformamide (200 mL, 2000 mmol), followed by potassium carbonate (20.7 g, 150 mmol) and methyl iodide (10.2 mL, 164 mmol). The reaction mixture was stirred for 10 hours at 23 °C. Ethyl acetate (1000 mL) was added, and the mixture was washed with water and brine. Organic layer was dried over sodium sulfate. Removal of solvent gave a crude solid product, which was treated with DCM and hexanes. The solid was collected and washed with hexanes (27.Og, 100percent). To a round bottom flask was added 5-hydroxy-2-nitrobenzaldehyde, 5 (15.6g, 93.3mmol) and DMF (200mL) followed by potassium carbonate (12.8g, 96.9mmol) and methyl iodide (5.35mL, 102.6mmol) and the mixture was stirred at RT overnight. The reaction mixture was partitioned between ethyl acetate and water. The separated organic layer was dried with sodium sulfate and concentrated to obtain 16g of 5-methoxy-2-nitrobenzaldehyde in quantitative yield. To 5-methoxy-2-nitrobenzaldehyde (10.3g, 56.9mmol) in a round bottom flask was added ethylene glycol (4.49mL, 79.6mmol) and catalytic amounts of p-toluene sulfonic acid monohydrate (490mg) and toluene (100mL) and the flask was fitted with a Dean-Stark apparatus and the mixture was heated to 100In a 50 mL round bottom flask 0.668 g (4 mmol) was addedHydroxy-2-nitrobenzaldehyde, 400 μL (6 mmol)Of methyl iodide, 0.832 g (6 mmol) of potassium carbonate and 10 mL of N, N-dimethylformamide, The reaction was stirred at room temperature for 8h, After the reaction was completed, the reaction mixture was poured into an ice-water mixture, After the ice melted and extracted three times with dichloromethane, the organic phase was collected, Washed three times, saturated sodium bicarbonate solution and brine washed once with water, dried over anhydrous sodium sulfate, concentrated under reduced pressure to remove the organic solvent to give a yellow solid as5-Methoxy-2-nitrobenzaldehyde (0.52 g, 100percent).Example 348 : Synthesis of (1E, 6E)-1-(4-hydroxyphenyl)-7-(5-methoxy-2-nitrophenyl)hepta-1, 6-diene-3, 5-dione (CU481); (1) Synthesis of 5-methoxy-2-nitrobenzaldehyde; To a solution of 5-hydroxy-2-nitrobenzaldehyde (300 mg, 1.80 mmol) in 3.6 mL of dry N, N-dimethylformamide was added sodium hydride (94 mg, 55percent, 2.1 mmol) under nitrogen at 0°C. After the solution was stirred at room temperature for 30 min, methyl iodide (0.17 mL, 2.7 mmol) was added with additional stirring for 30 min. The reaction mixture was quenched with saturated NHTo a solution of 5-hydroxy-2-nitrobenzaldehyde (300 mg, 1.80 mmol) in 3.6 mL of dry N, N-dimethylformamide was added sodium hydride (94 mg, 55percent, 2.1 mmol) under nitrogen at 0° C.To a stirred suspension of NaH (60percent, 431 mg, 10.8 mmol) in dry DMF (30.0 mL) was added a solution of 3-hydroxy-6-nitrobenzaldehyde (Sigma-Aldrich, 1.50 g, 8.98 mmol) in dry DMF (10.0 mL) dropwise followed by MeI (671 μL, 10.8 mmol) at 0 °C under NTo a solution of intermediate 37 (1.44 g, 7.9 mmol) in anh. CH2CI2 (40 mL) at r. t. , under N2, was added Dess-Martin periodinane (3.68 g, 1.1 eq). The reaction mixture was stirred for 3 HR AT r. t. , then sat. aq. Na2S203 (5 mL) and sat. aq. NaHCO3 (20 mL) were added. The phases were separated and the aqueous layer was extracted with EtOAc (2X100 mL). The combined organic extracts were dried over anh. NA2SO4, the solids were filtered and the solvent evaporated to dryness to give 1.45 g (100percent) of the title compound. NMR (1H, CDCI3) : 8 10.47 (s, 1H), 8.14 (d, 1H), 7.31 (d, 1H), 7.13 (dd, 1H), 3.94 (s, 3H).Example 8: 5-Methox -2-nitrobenzaldehydeTo the solution of (5-methoxy-2-nitrophenyl)methanol (18 g, 0.098 mol) in anhydrous DCM (0.2 L) was added PDC (11.5 g, 0.147 mol, 1.5 eq) and 4A MS (120 g) in portions. The mixture was stirred at room temperature for 16 h, filtered through a Celite pad. The filtrate was evaporated to dryness in vacuum to afford 5-methoxy-2- nitrobenzaldehyde (10 g, yield: 57percent) as a light yellow solid. 1HNMR (400 MHz, DMSO- d

Molecular Weight:181.15
XLogP3:1.3
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