Methyl 4-amino-2-methoxybenzoate

Grey Solid

The hydrogenation of methyl 2-methoxy-4-nitrobenzoate (700 mg, 3.3 mmol) in methanol (10 mL) catalyzed by 5percent Pd—C (100 mg) and NaTo a solution of methyl 2-methoxy-4-nitrobenzoate (10.0 g, 0.047 mol) in MeOH (100 mL) was added Pd/C (4.0 g, 10 percent w/w) under a nitrogen atmosphere in anautoclave and the reaction mixture was stirred at 45 psi (hydrogen atm) at room temperature for 12 h. The reaction mixture was passed through a Celite pad and the pad was washed with excess ethyl acetate. The filtrate was evaporated to dryness under reduced pressure to afford methyl 4-amino-2-methoxybenzoate (8.6 g, 0.048 mol, 99 percent yield) as a brown solid. ‘H NMR (400 MHz, DMSO-d6) ö 7.52 (d, J 8.4Hz, 1H), 6.32 (s, 1H), 6.23-6.25 (m, 1H), 5.6 (bs, 2H), 3.72 (s, 3H), 3.67 (s, 3H); LCMS (ESI) m/e 182.2 [(M+H), calcd for C9H12N03, 182.07]; LC/MS retention time (method B): ti = 0.87 mm.To a solution of methyl 2-methoxy-4-nitrobenzoate (12.00 g, 56.86 mmol) in methanol (100 mL) at room temperature under nitrogen was added 10percent palladium on carbon (4.88 g, 4.61 mmol). The resultant mixture was stirred under hydrogen (45 psi) for 12 h at room temperature. After the completion of reaction, the mixture was filtered through a diatomaceous earth (Celite®) pad and the filtrate was concentratedunder reduced pressure to afford methyl 4-amino-2-methoxybenzoate (10 g, 97percent yield) as a yellow solid: LCMS (ESI) m/e 182.2 [(M+H), calcd for C9H12N03, 182.1]; LC/MS retention time (method B): tp. = 0.87 min.(1) the bottle in the four port by adding 2 kg (13.06mol) P-amino-salicylic acid and 2.3 kg (40.10mol) grind garrulous potassium hydroxide, then adding 6 liter acetone solution, and strongly stirring. The temperature dropped to 25 °C, began to gradually dropwise 3 + (31.68mol) of sulfuric acid dimethyl ester. After dropping, to continue reaction 5.5 hours. Reaction-end splines, in addition to evaporating the solvent, and by adding 8 liters of water to dissolve, then using 25 liter of ethyl acetate extracted three times, the final combined ethyl acetate, drying the spin vaporization 2.18 kg of 4-amino-2-methoxy-benzoic acid methyl ester, in the yield of 92.1percent.1.1) After adding acetone (118.2 g, 20.37 mol) to a 500 mL three-necked flask, Further adding p-aminosalicylic acid (15.3 g, 0.1 mol) and sodium hydroxide (15.12 g, 0.27 mol), and stirring uniformly to obtain a mixture A;1.2) dimethyl sulfate (32.35g, 0.257mol) was added dropwise to the mixture A obtained in the step 1.1), after the completion of the dropwise addition, the mixture B was obtained;1.3) The mixture B is placed under room temperature conditions, after 6h to obtain a mixture C;1.4) The mixture C obtained in step 1.3) is filtered, the solid obtained after filtration is washed and dried to obtain compound II (yield 92.82percent);The washing process is: first washing with a 5percent sodium hydrogen carbonate solution, Use water again for washing4-Amino salicylic acid (VI) (2 kg) was added in acetone (12 lit) under stirring. Tetrabutyl ammonium bromide (2.09 kg) was added followed by addition of potassium hydroxide (2.18 kg) and the reaction mass was stirred. To the reaction mass dimethyl sulphate (3.89 kg) was added dropwise at 25-35°C. Stirring was continued at 25-35°C for 60 min. Reaction mass was quenched in prechilled water (30 Lit) at 0-5°C. Reaction mass was stirred and solid obtained by filtration under suction. Solid was washed with water and dried under suction. The wet solid was leached with methanol (2 Lit) at 60-65°C. The reaction mass was cooled to 0-5°C and solid was obtained by filtration, dried under vacuum.Yield : 72percentPurity: 98percent[0541| To a stirred solution of 269-1 (20.0 g, 130.68 mmol) in acetone (400 mL) was added KOH (18.4 g, 15 mmol) and (CHStep b) 4-amino-2-methoxy-benzoic acid methyl ester Step b) 4-amino-2-methoxy-benzoic acid methyl ester 2.9 g of 4-amino-2-methoxy-benzoic acid (77.17 mmol) was dissolved in 200 mL MeOH. At 0° C., to this solution was added 2 eq SOCl2 (12.5 mL, 154.24 mmol) The reaction mixture was heated to reflux temperature overnight. After solvent and excess of SOCl2 were removed under reduced pressure, the residue was suspended in 10percent Na2CO3. The precipitate that formed was solution was filtered and filter cake was washed with cold water until the washing became neutral. The product was then dried under vacuum at 50° C. About 12.04 g product was obtained after drying (86percent). M+H+(182).

An intermediate in the synthesis of Metoclopramide

Molecular Weight:181.19
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:181.07389321
Monoisotopic Mass:181.07389321
Topological Polar Surface Area:61.6
Heavy Atom Count:13
Complexity:184
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes