Methyl3-hydroxy-4-nitrobenzoate

3-Hydroxy-4-nitrobenzoic acid (10) (5.10 g, 27.85 mmol) was dissolved in MeOH (43 mL) and cooled to 0 °C. SOCl2 (3.20 mL, 43.69 mmol) was slowly added and the reaction mixture was stirred under refluxing conditions for 17 hours. The residual oil was redissolved in MeOH and concentrated (4x in order to remove the excess of SOCl2), to yield the title compound S1 (5.49 g, 27.85 mmol, quantitative) as a yellow solid.Concentrated sulfuric acid (0.5 mL) was added slowly to a solution of 3-hydroxy-4-nitrobenzoic acid (18) (1.88 g, 10.3 mmol) in methanol (not dried, HPLC grade, 60 mL) and the solution was heated under reflux for 18 h. Sodium bicarbonate was added and the solvent was removed under reduced pressure. Water and ethyl acetate were added to the residue and the aqueous layer was separated. The aqueous layer was extracted five times with ethyl acetate. The combined organic layers were washed twice with brine, dried over magnesium sulfate and the solvent was removed under reduced pressure to afford methyl 3-hydroxy-4-nitrobenzoate (19) as yellow crystals, yield: 2.00 g (99percent), mp 89.5-90.5 °C (lit.: 86-88 °C, Step 1: General Procedure for Benzoic Acid Fischer Esterification 3-Hydroxybenzoic acid (8.00 mmol) was dissolved in MeOH (60 mL) in a two-neck 250 mL round- bottom flask fitted with a reflux condenser and stir bar. Cone. HIn a 1L of reaction flask add 3-hydroxy-4-nitrobenzoic acid(25.0g0. 137mol) and Methanol (400mL) stirred and dissolved.Then add concentrated sulfuric acid (3mL) and was heated under reflux for 5hours. After the completion of the reaction , cooled to room temperature then dropwise added Saturated sodium bicarbonate solution to neutralizes. Concentratedunder vaccum rotary evaporation to dryness, then todissolve add ethyl acetate(500mL), washed with Saturated brine (2 x 300 mL) and dried over anhydrous sodiumsulfate, Filtered, and under reduced pressure the filtrate was concentrated by rotaryevaporation to dryness to give a yellow solid, 3-hydroxy- 4-nitrobenzoate (26.8g): Yield 99.6percent, melting point 86 ~ 88 ° C;General procedure: To a solution of 4-hydroxy-3-nitrobenzoic acid (25.0 g, 0.13 mol) in MeOH (150 mL) was added concd HStep 1 Methyl 3-hydroxy-4-nitro-benzoate; 3-Hydroxy-4-nitro-benzoic acid 1a(3.17 g, 17.32 mmol) was dissolved in 40 mL of anhydrous methanol. The reaction solution was cooled down to 0°C and added dropwise with thionyl chloride (3.09 g, 25.98 mmol) with stirring. Upon the completion of the addition, the resulting solution was heated to reflux for 2 hours. The reaction solution was concentrated under reduced pressure, extraceted with ethyl acetate (200 mL). The combined organic phase was washed with saturated sodium bicarbonate solution (100 mL.x.3), saturated sodium chloride solution (100 mL.x.3) successively, then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure to obtain the title compound methyl 3-hydroxy-4-nitro-benzoate 1b (3.30 g as a yellow solid) yield: 96.7percent. MS m/z (ESI): 195.8 [M-1]Step 13-Hvdroxy-4-nitro-benzoic acid methyl ester (41a); To a suspension of 3-hydroxy-4-nitrobenzoic acid (1) (5.00 g, 27.3 mmol) in methanol (150 mL) cooled on ice bath thionyl chloride (5.90 mL, 81.9 mmol) was added dropwise. The mixture was stirred at rt for 15 h upon which a clear solution formed. The solvent was evaporated under reduced pressure. To the residue petroleum ether (50 mL) was added, the obtained suspension was sonicated, filtered and washed with petroleum ether (20 mL). The purification was repeated twice and the residue was dried to give compound 2 (4.92) as yellow crystals. 4.8.1.1. Methyl 3-hydroxy-4-nitrobenzoate (2) [40]. Yellow crystals; yield 92percent (4.92 g); mp 87-88 °C (86-88 °C, lit [40]). IR (ATR)ν 3309, 3053, 2961, 1720, 1623, 1586, 1434, 1321, 1220, 1146, 1097, 966, 842, 798, 743, 667 cm3-Hydroxy-4-nitromethylbenzoate

Molecular Weight:197.14
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:197.03242232
Monoisotopic Mass:197.03242232
Topological Polar Surface Area:92.4
Heavy Atom Count:14
Complexity:236
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes