METHYL(2-NITRO-PHENYL)-ACETATE

(A) Step 1: protecting group 2, 2 - dimethyl - (2' - nitro) phenylacetyl (DMNA) preparation, under ice bath, the 10g O-nitrophenyl acetic acid dissolved in 200 ml methanol solution, then slowly adding 30 ml thionyl chloride, under ice bath, the reaction 30 minutes, TLC monitoring completion of the reaction, the crude product of concentrating under reduced pressure, column chromatography ortho-nitrophenyl-acetic acid methyl ester 10g, yield 93percent;A. Preparation of Methyl 2-(2-nitrophenyl)acetate (Compound 1-2)[00213j To a solution of Compound 1-1 (18.1 g, 100 mmol) in methanol (150 mL) at room temperature was added sulfurous dichloride (SOC12, 13.1 g, 110 mmol) dropwise. The mixture was heated to 60 °C and stirred for 30 minutes. The reaction mixture was concentrated to give a pale yellow oil, diluted with ethyl acetate (200 mL), washed with sodium bicarbonate (sat. aq., 150 mL x 3), brine (100 mL x 2), dried over anhydrous sodium sulfate, concentrated to give the desired product Compound 1-2 (19.1 g, yield: 98percent) as a pale yellow oil. MS (ES): mlz: 196[M+H]. ‘H NMR (400 MHz, CDC13) ö: 8.12 (dd, 1H, J= 8.4, 1.2 Hz), 7.61 (m, 1H), 7.49 (m, 1H), 7.36 (d, 1H, J= 7.6 Hz), 4.04 (s, 2H), 3.72 (s, 3H).Preparation of methyl 2-(2-nitrophenyl)acetate (Compound 11-2)[00268j To a solution of 2-(2-nitrophenyl)acetic acid (Compound 11-1, 18.1 g, 100 mmol) in methanol (150 mL) at room temperature was added sulfurous dichloride (50C12, 13.1 g, 110 mmol) dropwise. The mixture was heated to 60 °C and stirred for 30 minutes. The reaction mixture was concentrated to give a pale yellow oil, diluted with ethyl acetate (200 mL), washed with sodium bicarbonate (sat. aq., 150 mL x 3), brine (100 mL x 2), dried over anhydrous sodium sulfate, concentrated to give the desired product methyl 2-(2-nitrophenyl)acetate (Compound 11-2, 19.1 g, yield: 98percent) as a pale yellow oil. MS (ESI): mlz: 196[M+H]. ‘H NMR (400 MHz, CDC13) ö: 8.12 (dd, 1H, J= 8.4, 1.2 Hz), 7.61 (m, 1H), 7.49 (m, 1H), 7.36 (d, 1H, J= 7.6 Hz), 4.04 (s, 2H), 3.72 (s, 1H).To a solution of 2-nitrophenyl acetic acid (5 g, 0.0276 mol) in DCM (50 rnL) was added DMAP (1 eq, 3.37 g) followed by DCC (1 eq, 5.63 g) and methanol (5 eq, 5.58 mL) was added last. The reaction mixture was stirred 2-3h, the TLC shows when the reaction was completed. After that the reaction was filtered to remove the DCU formed and the filtrate was washed with 0.1N HCl (2x 25 mL), satured aqueous sodium bicarbonate solution (2x 25mL) and water (2x 25mL), dried over sodium sulfate and the solvent remove under reduced pressure. The crude ester was purified by flash chromatography (DCM: EA 60: 40), to yield the product as a yellow oil 4.8 g (90percent): Methyl phenylacetate (45 g, 0.3 mol), Dichloromethane (1500 mL) was placed in a dry reaction flask.Stir vigorously at 0 °C, A solution of fuming nitric acid (189 g, 3 mol) and dichloromethane (462 mL) was slowly added dropwise.After the addition was completed, the temperature was raised to room temperature and stirring was continued for 24 hours.The reaction was monitored by TLC.After the reaction is completed, the reaction solution is washed with water to neutrality.The organic phase was washed with sodium sulfate solution (10percent).concentrate, The light yellow liquid was obtained by distillation under reduced pressure to Intermediate 2 (49.2 g, 84percent).(Step 1) Example 14: Carbonylation of 2-nitro benzyl bromideusing Compound 2IIA as a catalyst; 2-Nitro-benzyl bromide (268cmTo a solution of compound 13 (1.82 g, 9.32 mmol) in toluene (15 mL)was added 37% formaldehyde aqueous solution (2.35 g, 26.1 mmol), tetrabutylammonium iodide (138 mg, 0.37 mmol), and potassium carbonate (3.86 g, 28.0 mmol) at room temperature. The resulting mixture was stirred for 12 h at80 C.After cooling to room temperature, water (15 mL) was added, and the aqueoussolution was extracted with toluene (2 20 mL). The combined organic extracts were dried overanhydrous magnesium sulfate, filtered and concentrated under reduced pressure.Purification was achieved by ISCO chromatography (1:3::ethyl acetate:hexanes)to methyl 2-(2-nitrophenyl)acrylate (14)as a pale yellow oil (1.64 g, 85% yield); Rf = 0.32 (1:4::EtOAc:hexanes;, LC/MS m/z 208 (M++1);1H NMR (300 MHz, CDCl3) delta 8.12 (dd, J = 1.2, 8.1 Hz, 1H), 7.64 (dt, J = 1.5, 7.5 Hz, 1H), 7.53 (dt, J = 1.5, 8.1 Hz, 1H), 7.39 (dd, J = 1.5, 7.5 Hz, 1H), 6.55 (d, J= 0.6 Hz, 1H), 5.88 (d, J = 0.9 Hz, 1H), 3.73 (s, 3H).General procedure: A soln of the appropriate nitroarene (1 equiv), Ru(bpy)3Cl2·6H2O(0.025 equiv), CSA (0.10 or 1.0 equiv), and dihydropyridine 5 (2.1, 3.0, or 4.0 equiv) in DMF (0.1 M) was placed in a sealed 25-mL Schlenk flask. The soln was degassed using three freeze-pump-thaw cycles and then irradiated using a household 20-W compact fluorescent light bulb. After 16 h, the reaction was diluted with EtOAc, then washed with 1 M HCl (2 ×). The aqueous phases were extracted with EtOAc, and the organic phases were combined and washed with brine (1 ×), dried (MgSO4), and concentrated in vacuo. A soln of Boc2O (1.1 or 2.2 equiv), Et3N (5.0 equiv), and THF (0.05 M) was added. After 2-24 h, the mixture was concentrated in vacuo and purified by column chromatography.

Molecular Weight:195.17
XLogP3:1.9
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:195.05315777
Monoisotopic Mass:195.05315777
Topological Polar Surface Area:72.1
Heavy Atom Count:14
Complexity:223
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes