Benzoic acid, 3-amino-4-fluoro-, methyl ester

Step B: Methyl 3-amino-4-fluorobenzoate; To a solution of methyl 4-fluoro-3-nitrobenzoate (6.57 g, 33 mmol) in EtOAc (75 mL) was added 10percent palladium on carbon (0.66 g). The suspension was transferred to a Fisher-Porter flask and installed in a hydrogenation apparatus. The flask was charged with HTo a stirring solution of 4-fluoro-3-nitrobenzoic acid (25 g, 126 mmol) in MeOH (20 mL) was added Fe (28 g, 502 mmol), followed by addition of con. HCl (5 mL). The mixture was heated to reflux for two days, cooled to room temperature, and then filtered. The filtrate was concentrated in vacuo to give the desired product as a solid (15 g, 68percent). LC-MS (ES) m/z = 170.1 (M+H)To a stirred solution of 3-amino-4-fluoro-benzoic acid (25 g, 161 mmol) in methanol (300 mL) was added thionyl chloride (30 mL, 403 mmol) dropewise at 0° C. Then the mixture solution was refluxed for 12 hours before cooling to room temperature. Then the reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (500 mL), washed with saturated aqueous sodium bicarbonate solution (3.x.100 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to afford 3-amino-4-fluoro-benzoic acid methyl ester (27.5 g, quant.) as a pale-white solid: LC/MS m/e calcd for CStep 1: 3-amino-4-fluorobenzoic acid (0.5g) was dissolved in methanol (lOml), then concentrated sulfuric acid (lml) was added. The reaction solution was heated to reflux until the reaction is complete. Then the reaction mixture was cooled down and poured into water, the pH of the resultant solution was adjusted to 8 by 2N NaOH solution. The product was extracted to EtOAc layer and the solvent was stripped off. 290mg of methyl 3-amino-4- fluorobenzoate was obtained.General procedure: To a solution of 3-nitromethyl benzoate (26.0 g, 144 mmol) in methanol (300 mL) was added Pd/C (2 g, 18.79mmol), the mixture was stirred under H2 at rt overnight. The reaction mixture was filtered through a Celite pad , the filtrate was concentrated in vacuo to get the title compound as a yellow oil (21.7 g, 100percent).To a suspension of compound 21 (1.01 g, 6 mmol) in hydrochloric acid (13 ml, 37%) at 0 C was added a cold solution of sodium nitrite (0.50 g, 7.2 mmol) in water (5 ml) maintaining the temperature below 5 C. The resultant solution was stirred in an ice bath for 30 min before the addition of a solution of tin(II) chloride dihydrate (4.06 g, 18 mmol) in hydrochloric acid (5 ml, 37%) maintaining the temperature below 5 C. The resultant suspension was stirred at 0 C for 3 h and the suspension filtered and then dissolved in DCM, washed with saturated NaHCO3, dried over by MgSO4 to get the compound 22 (1.01 g, 92%). 1H NMR (CDCl3, 400 MHz): delta 7.79-7.77 (m, 1H), 7.46 (s, 1H), 7.04-6.99 (m, 1H), 5.48 (br, 1H), 3.91 (s, 3H) 3.62 (br, 2H). ESI-HRMS: m/z calcd for C8H9FN2O2 [M+H]+ 185.0682 found 185.0664.

Molecular Weight:169.15
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:169.05390666
Monoisotopic Mass:169.05390666
Topological Polar Surface Area:52.3
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes