Benzoic acid, 3-(trifluoromethyl)-, methyl ester

CLEAR SLIGHTLY YELLOW LIQUID

REFERENCE EXAMPLE 70 Dimethyl 2-m-trifluoromethylphenyl-2-oxoethylphosphonate (70) STR89 A solution of n-butyl lithium in hexane (1.58N, 38.8 ml, 61.3 mmol) was added dropwise under argon atmosphere to a stirred solution of dimethyl methylphosphonate (7.6 g, 61.3 mmol) in 100 ml of anhydrous THF at -78 C. After 30 minutes, methyl m-trifluoromethylbenzoate (5.0 g, 24.5 mmol) was added dropwise and the mixture was stirred for 30 minutes. The reaction mixture was allowed to warm to 0 C., diluted with 3.7 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue and the mixture was extracted with ethyl acetate (50 ml*2). The combined ethyl acetate layers were washed with water (20 ml*1) and brine (20 ml*1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give an oil of dimethyl 2-m-trifluoromethylphenyl-2-oxoethylphosphonate (4.72 g, 15.9 mmol, yield 65%, b.p. 198-202 C./0.06 mmHg), which was assigned the structure by the following data: IR(Liquid film method): 3450, 3070, 2860, 1680, 1610, 1590, 1440, 1405, 1330, 1305, 1250, 1165, 1120, 1090, 1065, 1030, 920, 875, 840, 825, 800, 755, 730, 690, 650 cm-1. NMR(90 MHz, CDCl3, delta): 3.65(2H, d, J=22.9 Hz), 3.78(2H, d, J=11.2 Hz), 7.5-7.9(2H, m), 8.1-8.35(2H, m).The specific synthesis method is: 38.8 g (0.2 mol) of m-trifluoromethylbenzoic acid was added to the reactor, and 170 g of cyclohexane was used. After the alkane was dissolved, 15 g of methanol was added, and 4 g of a cationic acid resin catalyst was added thereto to stir, and the temperature was raised to reflux reaction, and the water produced by the system was taken out in time. After the reaction is completed, the catalyst is cooled and filtered, and the organic solvent is distilled off under negative pressure. After the solvent is evaporated, the methyl trifluoromethylbenzoate is colorless and transparent, and the content is 99.6%, and the yield is 95.8%.Intermediate l g: methyl S-ftrifluoromethyDbenzoate. To a solution of 3- (trifluoromethyl)benzoic acid (5 g, 26.30 mmol, 1.00 equiv) in methanol (25 mL) was added dropwise thionyl chloride (9.39 g, 78.93 mmol, 3.00 equiv) and the resulting solution was stirred for 2 h at 75C in an oil bath. The mixture was concentrated under vacuum, diluted with 100 mL of ethyl acetate and then washed with 2x30 mL of sodium carbonate and 2x30 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to yield 4.6 g (86%) of methyl 3- (trifluoromethyl)benzoate as yellow oilGeneral procedure: A catalytic amount of concentrated H2SO4 wasadded to a solution of carboxylic acids 16(a-j) (1.0 mmol)in 50 mL of methanol, and the mixture was refluxed for 6 h. It was allowed to cool. The saturated solution ofNaHCO3 was added to the reaction mixture, and it wasextracted with EtOAc (2 X 50 mL). The combined organiclayer was dried Na2SO4 and concentrated to obtain puremethyl esters 17(a-j).General procedure: To a solution of 5.0 mmol of dierent substituted benzoic acids (1a~1p, 1s, and 1t), nicotinic acid(1q) or 2-phenylacetic acid (1r) in MeOH (15 mL) was added sulfurous dichloride (2 mL), then the mixture was allowed to reach 40 C and stirred for 1 h. The resulting solution was concentrated andpartitioned between sodium bicarbonate solution (PH 7~8) and ethyl acetate (3). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated to yield the correspondingesters (2a~2t) in 89%-96% yields, which were taken up for the next step without any purification.

Molecular Weight:204.15
XLogP3:3.3
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:204.03981395
Monoisotopic Mass:204.03981395
Topological Polar Surface Area:26.3
Heavy Atom Count:14
Complexity:213
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes