4-BROMO-2-HYDROXYBENZONITRILE

white crystalline

A mixture of 2-fluoro5-bromobenzonitrile (30 g, 152.3 mmole), potassium acetate (222.4 g, 228.5 mmol), and 18-crown-6 ether (60.4 g, 288.5 mmol) in MeCN (400 mL) was heated at reflux in 36 h. The mixture was cooled, 2.5 N NaOH (200 mL) added, and stirred at RT overnight. The mixture was extracted with ether (discarded). The aqueous layer was acidified with 6N HCl, extracted with EtOAc, dried over MgSO4, concentrated, purified by flash column chromatography (40percent EtOAc/Hex) to give the above titled compound as a light yellow foam (24.45 g, 81percent). NMR(300 MHz, DMSO-d6): 7.13(dd, J=1.7, 8.3 Hz, 1H), 7.17(d, J=1.7 Hz, 1H), 7.61(d, J=8.3 Hz, 1H).To a stirred solution of 4-bromo-2-methoxy-benzonitrile (4. 60 g, 21.7 MMOL) in methylene chloride (20 mL) was added aluminum chloride (14.5 g, 108 MMOL). After stirring under an argon atmosphere for 10 min, more methylene chloride (30 mL) was added, and the mixture left to reflux under argon overnight. The reaction was then diluted with ethyl acetate, washed with water, brine, and dried over magnesium sulfate. The solvent was removed at reduced pressure, providing (4.09 g, 95.2percent) of 4-bromo-2- hydroxy-benzonitrile as a slightly gray-colored PRODUCT. H-NMR (CDC13) 8 7.35 (d, J = 8.4 Hz, 1 H), 7.19 (d, J = 1.4 Hz, 1H), 7.14 (dd, J = 8. 4, 1, 4 HZ, 1 H), 6.15 (s, 1H) ; TLC RF = 0.78 (50percent ethyl acetate-hexane).Step 2: Preparation of the intermediate: 4-bromo-2-hydroxy-benzonitrile; To a stirred solution of 4-bromo-2-methoxy-benzonitrile (4. 60 g, 21.7 mmol) in methylene chloride (20 mL) was added aluminum chloride (14.5 g, 108 mmol). After stirring under an argon atmosphere for 10 min, more methylene chloride (30 mL) was added, and the mixture left to reflux under argon overnight. The reaction was then diluted with ethyl acetate, washed with water, brine, and dried over magnesium sulfate. The solvent was removed at reduced pressure, providing (4.09g, 95.2percent) of 4-bromo-2- hydroxy-benzonitrile as a slightly gray-colored product. 1H-NMR (CDCI3) 6 7.35 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 1.4 Hz, 1H), 7.14 (dd, J = 8. 4, 1, 4 Hz, 1H), 6.15 (s, 1H) ; TLC Rf = 0.78 (50percent ethyl acetate-hexane).Step 2: Preparation of the intermediate: 4-bromo-2-hvdroxy-benzonitrile. To a stirred solution of 4-bromo-2-methoxy-benzonitrile (4.60 g, 21.7 mmol) in methylene chloride (20 mL) was added aluminum chloride (14.5 g, 108 mmol). After stirring under an argon atmosphere for 10 min, more methylene chloride (30 mL) was added, and the mixture left to reflux under argon overnight. The reaction was then diluted with ethyl acetate, washed with water, brine, and dried over magnesium sulfate. The solvent was removed at reduced pressure, providing (4.09g, 95.2percent) of 4-bromo-2-hydroxy-benzonitrile as a slightly gray-colored product. a A mixture of 2-fluoro5-bromobenzonitrile (30 g, 152.3 mmole), potassium acetate (222.4 g, 228.5 mmol), and 18-crown-6 ether (60.4 g, 288.5 mmol) in MeCN (400 mL) was heated at reflux in 36 h. The mixture was cooled, 2.5 N NaOH (200 mL) added, and stirred at RT overnight. The mixture was extracted with ether (discarded). The aqueous layer was acidified with 6N HCl, extracted with EtOAc, dried over MgSO4, concentrated, purified by flash column chromatography (40% EtOAc/Hex) to give the above titled compound as a light yellow foam (24.45 g, 81%). NMR(300 MHz, DMSO-d6): 7.13(dd, J=1.7, 8.3 Hz, 1H), 7.17(d, J=1.7 Hz, 1H), 7.61(d, J=8.3 Hz, 1H).To a stirred solution of 4-bromo-2-fluorobenzonitrile (4.0 g, 20 mmol) in DMF (20 mL) was added 2-(methylsulfonyl)ethanol (3.7 g, 30 mmol) and then NaH (2.4 g, 60 % in mineral, 60 mmol) in portions at 0 C. The mixture was then warmed to rt. and quenched with 1N HCl, and extracted by EtOAc. The organic layers were washed with brine and dried over sodium sulfate, concentrated to give

Molecular Weight:198.02
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:196.94763
Monoisotopic Mass:196.94763
Topological Polar Surface Area:44
Heavy Atom Count:10
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes