BENZOIC ACID, 4-BROMO-2-(HYDROXYMETHYL)-

5-Bromo phthalide (9 g, 0.042 mol) was refluxed with 2 (N) aqueous sodium hydroxide (100 ml) in methanol (150 ml) for overnight. Lithium hydroxide (3.45 g, 70.42 mmol, 3.0 eq) was added to a solution of 5-bromophthalide (5.0 g, 23.47 mmol, 1.0 eq) in THF/MeOH/ HCompound I (15.0 g) was added to 2N aqueous lithium hydroxide solution (105 mL), and the mixture was stirred at room temperature for 3 hours. 6-Bromo-3H-isobenzofuran-1-one (5.0 g, 23.47 mmol) was weighed and added to a three-neck bottle.Measure tetrahydrofuran: methanol: water (2:1:1, 80 mL), add to a three-neck bottle, stir for 10 minutes.After dissolution, lithium hydroxide (3.45 g, 70.42 mmol) was added and stirred at room temperature for 16 hours.After the reaction of the raw materials was monitored by thin layer chromatography, the reaction mixture was concentrated, and water (100 mL) was added.The pH was adjusted to 3 with 2N hydrochloric acid and extracted three times with 100 mL of ethyl acetate.The organic phase is then washed with water and the organic phase is washed with saturated sodium chloride.Dried over anhydrous sodium sulfate, filtered and concentrated.This gave 3.3 g (91percent) of a white solid.[0338j Lithium hydroxide (3.45 g, 70.42 mmol, 3.0 equiv) was added at room temperature over several minutes to a solution of 5-bromophthalide (5.0 g, 23.47 mmol, 1.0 equiv) in a 2:1:1 solution of THF/MeOH/ H20 (80 mL) and the reaction mixture was stirred at room temperature for 16 h. After removal of the solvent, the residue was diluted with water (100 mL), adjusted to pH = 3 with HC1 (2 N) and extracted with EtOAc (100 mL x 3). The organic layers were collected, dried (Na2SO4), filtered, and concentrated via rotary evaporator to give title product (3.47 g, yield: 94percent) as a white solid, which was used in the next step withoutfurther purification. ESI-MS (M+H) : 231.1. ‘H NMR (400 MHz, CD3OD) (5: 7.88-7.86 (m, 2H), 7.45 (dd, J= 8.4, 2.0 Hz, 1H), 4.90 (s, 2H).6-Bromo-3H-isobenzofuran-1-one (5.0 g, 23.47 mmol) was weighed and added to a three-neck bottle.Measure tetrahydrofuran: methanol: water (2:1:1, 80 mL), add to a three-neck bottle, stir for 10 minutes.After dissolution, lithium hydroxide (3.45 g, 70.42 mmol) was added and stirred at room temperature for 16 hours.After the reaction of the raw materials was monitored by thin layer chromatography, the reaction mixture was concentrated, and water (100 mL) was added.The pH was adjusted to 3 with 2N hydrochloric acid and extracted three times with 100 mL of ethyl acetate.The organic phase is then washed with water and the organic phase is washed with saturated sodium chloride.Dried over anhydrous sodium sulfate, filtered and concentrated.This gave 3.3 g (91%) of a white solid.[0339j Sodium hydride (3.46 g, 86.56 mmol, 4.0 equiv) was added in small portions over the course of 0.5 h at room temperature to a mixture of Sodium hydride (3.46 g, 86.56 mmol, 4.0 eq) was added in small portions over the course of 0.5 h at rt to a mixture of Compound 13 (5.0 g, 21.64 mmol) and bromoacetic acid (2.99 g, 21.64 mmol) were weighed into a three-neck bottle.Measure tetrahydrofuran (60 mL), add to a three-necked bottle, stir for 10 minutes, dissolve, Sodium hydride (3.46 g, 86.56 mmol) was added portionwise over half an hour.Then sodium iodide (324.6 mg, 2.164 mmol) was added and stirred at 70 C for 16 hours.After thin layer chromatography was used to monitor the completion of the reaction, the temperature was lowered to room temperature, and water (150 mL) was added.The pH was adjusted to 3 with 2N hydrochloric acid and extracted three times with 100 mL of ethyl acetate.The organic phases are combined, then the organic phase is washed with water and the organic phase washed with saturated sodium chloride.Dry over anhydrous sodium sulfate, filter and concentrate to give 4.27 g (70%) of white solid.[0338j Lithium hydroxide (3.45 g, 70.42 mmol, 3.0 equiv) was added at room temperature over several minutes to a solution of 5-bromophthalide (5.0 g, 23.47 mmol, 1.0 equiv) in a 2:1:1 solution of THF/MeOH/ H20 (80 mL) and the reaction mixture was stirred at room temperature for 16 h. After removal of the solvent, the residue was diluted with water (100 mL), adjusted to pH = 3 with HC1 (2 N) and extracted with EtOAc (100 mL x 3). The organic layers were collected, dried (Na2SO4), filtered, and concentrated via rotary evaporator to give title product (3.47 g, yield: 94%) as a white solid, which was used in the next step withoutfurther purification. ESI-MS (M+H) : 231.1. 'H NMR (400 MHz, CD3OD) (5: 7.88-7.86 (m, 2H), 7.45 (dd, J= 8.4, 2.0 Hz, 1H), 4.90 (s, 2H).

Molecular Weight:231.04
XLogP3:1.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:229.95786
Monoisotopic Mass:229.95786
Topological Polar Surface Area:57.5
Heavy Atom Count:12
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes