4-cyano-3-methylbenzoic acid

To a solution of 4-bromo-2-methylbenzonitrile (2.0 g, 10.2 mmol) in THF (100 ml) at -78°C under a nitrogen atmosphere was added dropwise a 2.5 M solution of n-butyl lithium (4.48 ml, 11.2 mmol). The mixture was stirred at -78°C for 1h and then poured onto solid carbon dioxide (5 g) in THF (50 ml). The mixture was allowed to warm to room temperature. Water was added (200 ml) and the mixture was extracted with diethyl ether (3 times). The aqueous layer was acidified by addition of concentrated HCl and extracted with chloroform (3 times). The combined chloroform extracts were washed with water, dried over MgSO4, and concentrated in vacuo to give a white solid identified as 4-cyano-3-methylbenzoic acid (1.2 g, 73percent).Example B To a solution of 4-bromo-2-methylbenzonitrile (2.0g, 10.2mmol) in THF (100ml) at -78°C under a nitrogen atmosphere was added dropwise a 2.5M solution of n-butyl lithium (4.48ml, 11.2mmol). The mixture was stirred at -78°C for lh and then poured onto solid carbon dioxide (5g) in THF (50ml). The mixture was allowed to warm to room temperature. Water was added (200ml) and the mixture was extracted with diethyl ether (3 times). The aqueous layer was acidified by addition of concentrated HC1 and extracted with chloroform (3 times). The combined chloroform extracts were washed with water, dried over MgS0To a solution of 4-bromo-2-methylbenzonitrile (2.0 g, 10.2 mmol) in THF (100 ml) at -78° C. under a nitrogen atmosphere was added dropwise a 2.5M solution of n-butyl lithium (4.48 ml, 11.2 mmol).. Asolution of nBuLi in THF (2.5 M, 4.49 mL, 11.2 mmol) was added dropwise to astirred solution of 4-bromo-2-methylbenzonitrile (2.0 g, 10.2 mmol) in dry THF (100 mL) at −78° C. and the solution stirred at −78° C.for 1 h. A stream of dry CO2 was bubbled through the solution for 10 min andthe mixture warmed to 20° C. The mixture was diluted with water (100 ml) andwashed with Et2O (3×20 mL). The aqueous phase was acidified to pH 2 with cHCland extracted with CHCl3 (3×50 mL) and the organic fraction was dried and thesolvent evaporated to give crude acid 171 (1.05 g, 64percent)A solution of 2.5 M n-butyllithium in hexanes(6.7 mL, 16.8 mmol) was added to anhydrous THF (15 mL) at −78 °C. A solution of 4-bromo-2-methylbenzonitrile 21 (3.0 g, 15.3 mmol) in THF (15 mL) was then added dropwise and allowed to stir for 30 min. Dry ice (solid CO2) was added and the solution was allowed to stir 1 h while warming to room temperature. The reaction was then concentrated in vacuo and the resulting residue was triturated in ether and filtered. The solid was dissolved in EtOAc and washed with 2 M HCl and brine. The organic layer was isolated, dried over MgSO4, concentrated in vacuo, then triturated in ether/ hexane and dried under high vacuum. Obtained 4-cyano-3-methylbenzoic acid 22 (1.5 g, 60.8percent yield) as a white solid. To a -78EXAMPLE B Example C

Molecular Weight:161.16
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:161.047678466
Monoisotopic Mass:161.047678466
Topological Polar Surface Area:61.1
Heavy Atom Count:12
Complexity:228
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes