5-Bromo-2-hydroxybenzoic acid methyl ester

Intermediate III: 6- (aminomethyl)-2, 2-dimethyl-4H-1, 3-benzodioxin-4-one; Step a) Formation of methyl-5-bromosalicylate; To a solution of 5-BROMOSALICYLIC acid (200 G, 0.92 mol) in METHANE . (2 L) was added thionylchloride (440 g, 3.7 mol) at 0°C with stirring and then allowed to reflux at 70°C for 40H. Excess solvent was distilled off and to the crude residue was added EtOAc (2 L). The organic layer was washed with 10percent cold aqueous NAHC03 solution (2X1 L), brine and dried. The solvent was removed UNDER vacuum to give the title compound as a low melting point solid (190 g, 89percent). TLC: PetEther/EtOAc, 7:3, Rf: 0.6To a solution of 5-bromosalicylic acid (200 g, 0.92 mol) in methanol (2 L) was added thionylchloride (440 g, 3.7 mol) at 0°C with stirring and then allowed to reflux at 70°C for 40h. Excess solvent was distilled off and to the crude residue was added EtOAc (2 L). The organic layer was washed with 10percent cold aqueous NaHCO3 solution (2 x 1 L), brine and dried. The solvent was removed under vacuum to give the title compound as a low melting point solid (190 g, 89percent). TLC: PetEther/EtOAc, 7: 3, Rf: 0. 65-Bromo-2-hydroxybenzoic acid (2.17 g, 10 mmol) was dissolved in methanol (50 ml_) and sulfuric acid (100percent, 1 ml_) and heated at rx for 12 h. After cooling and neutralization (NaHCOREFERENCE To a solution of methyl salicylate S1(15.2 g, 0.1 mol) in dichloromethane (100 ml) was added dropwise bromine (1 N solution in dichloromethane, 1.1 equiv) for 6h, then concentrated, the residue was poured into the saturated sodium sulphite, The resulting yellow precipitate was recovered by filtration and washed with petroleum ether to obtain the light yellow solid S2. (yield: 98percent). Methyl paraben (152 g, 1 mol) was dissolved in chloroform (600 mL).Under ice-cooling, a solution of liquid bromine (176 g, 1.1 mol) in chloroform (300 mL) was carefully added dropwise. The dropping rate was controlled so that the temperature of the system was not higher than 10°C. After the addition, the system was slowly warmed to room temperature and stirred overnight. The reaction was monitored by TLC on the following day. After removing the solvent and excess bromine in vacuo, the system was dissolved in dichloromethane (1 L). Separately washed with water (1L), saturated aqueous sodium hydrogencarbonate solution, 1percent sodium dithionite solution, and water (1L), dried over anhydrous sodium sulfate, and the solvent was removed in vacuo to obtain a crude product. The crude product was recrystallized from methanol to give 201 g of white crystals in a yield of 87.4percent.General procedure: Reaction conditions: Thiourea (5.1 molpercent, 2 mg, 0.026 mmol) was added to an acetonitrile solution (10 mL) containing NBS (1.15 equiv, 104.4 mg, 0.587 mmol). Anisole (56.3 mg, 0.51 mmol) was added immediately to the resulting stirred solution and allowed to stir at room temperature for 10 min. The reaction was quenched by the addition of 10percent aqueous solution of Na(a) Example 114 Amethyl 5-bromo-2-hydroxybenzoate; To a solution of methyl 2-hydroxybenzoate (152 g, 1.0 mol) in chloroform (500 mL) was added dropwise with stirring a solution of bromine (172 g, 1.08 mol) in chloroform (300 mL) at 10° C. After the addition, the solution was stirred at room temperature overnight. The mixture was diluted with dichloromethane (500 mL), washed with water (1 L.x.3), saturated sodium bicarbonate solution (500 mL), brine (500 mL), dried over anhydrous sodium sulfate and concentrated to give crude product. The crude product was re-crystallized from methanol to give methyl 5-bromo-2-hydroxybenzoate (192 g, yield 83percent) as a white solid. [0312] Br2 (52 g) was slowly added to a stirred solution of methyl salicylate (50 g; 330 mmol) in 300 mL acetic acid. The reaction mixture was stirred at rt. for 10 h, poured onto ice-water and the precipitate recrystallized from MeOH, giving the sub-title compound in a 83percent yield.

Molecular Weight:231.04
XLogP3:3.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:229.95786
Monoisotopic Mass:229.95786
Topological Polar Surface Area:46.5
Heavy Atom Count:12
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes