METHYL 3-FLUOROPHENYLACETATE

clear colorless to slightly yellow liquid

General procedure: 5.1.57.1. Step 1. To a solution of 3-fluorophenylacetic acid (24.85 g, 158 mmol) in MeOH (200 mL) was added SOCl2 (4.00 mL, 52.2 mmol) at 0 C with silica gel blue tube. After stirring at rtfor 3 h, the reaction mixture was concentrated under reduced pressure.The residue was partitioned between 1 N NaOH (250 mL) andEtOAc (250 mL). The separable organic layer was washed withbrine (100 mL), dried over MgSO4, filtered, concentrated underreduced pressure to obtain methyl (3-fluorophenyl)acetate(25.81 g, 97percent) as colorless oil. 1H NMR (CDCl3) d 3.62 (2H, s), 3.71 (3H, s), 6.92–7.09 (3H, m), 7.29 (1H, ddd, J = 7.9, 7.7, 6.0 Hz);IR (KBr) cm1 3065, 3024, 3001, 2955, 2845, 1740, 1616, 1593, 1489, 1450, 1437, 1342, 1258, 1200, 1165, 1144, 1076, 1015, 955, 930.General procedure: To an appropriately substituted phenylacetic acid (10 mmol) dissolved in dried methanol (50 mL), concentrated sulfuric acid (0.5 mL) was added dropwise.The mixture was refluxed from 7 to 9 h. Next, the solvent was evaporated, and residue was dissolved in 40 mL of ethyl acetate, washed with 0.5percent NaOH andbrine. Organic layer was dried over anhydrous Na2SO4 and filtered. The solvent was evaporated to give the products as colorless oils.Methyl 2-(3-fluorophenyl)acetate (1.90 g, 11.3 mmol) and N-bromo succinimide (2.01 g, 11.3 mmol) are dissolved in CCl4 (80 mL). HBr (64 ul, 0.56 mmol) is added and the mixture is stirred under reflux overnight. The mixture is cooled at RT, diluted with DCM and washed with sat. NaHCO3, water and brine.The organic layer is dried (Na2SO4), filtered and evaporated obtaining intermediate 1144 as a yellow oil (2.68 g, 96% yield).Methyl 2-(3-fluorophenyl)acetate (1.90 g, 1 1.3 mmol) and N-bromo succinimide (2.01 g, 1 1.3 mmol) were dissolved in CC14 (80 ml). HBr (64 ul, 0.56 mmol) was added and the mixture was stirred under reflux overnight. The mixture was cooled at room temperature, diluted with DCM and washed with sat. NaHCO3, water and brine. The organic layer was dried (Na2SO4), filtered and evaporated obtaining intermediate 115 (2.68 g, 96% yield).General procedure: 5.1.57.1. Step 1. To a solution of 3-fluorophenylacetic acid (24.85 g, 158 mmol) in MeOH (200 mL) was added SOCl2 (4.00 mL, 52.2 mmol) at 0 C with silica gel blue tube. After stirring at rtfor 3 h, the reaction mixture was concentrated under reduced pressure.The residue was partitioned between 1 N NaOH (250 mL) andEtOAc (250 mL). The separable organic layer was washed withbrine (100 mL), dried over MgSO4, filtered, concentrated underreduced pressure to obtain Dissolve 3-fluorophenylacetic acid (3.1 g, 20 mmol) in 60 mL of methanol, and add 2 mL of concentrated sulfuric acid.The reaction temperature was raised to 60 C, and the reaction was carried out for 10 hours. The reaction system was concentrated, and the obtained residue was dissolved in 100 mL of ethyl acetate; then washed with water (30 mL x 3), and dried over anhydrous sodium sulfate for 1 h.Filtration and concentration of the filtrate were separated by silica gel column chromatography [petroleum ether / ethyl acetate (v / v) = 30: 1], The target product was obtained (colorless liquid, 2.9 g, yield: 86.3%).General procedure: To an appropriately substituted phenylacetic acid (10 mmol) dissolved in dried methanol (50 mL), concentrated sulfuric acid (0.5 mL) was added dropwise.The mixture was refluxed from 7 to 9 h. Next, the solvent was evaporated, and residue was dissolved in 40 mL of ethyl acetate, washed with 0.5% NaOH andbrine. Organic layer was dried over anhydrous Na2SO4 and filtered. The solvent was evaporated to give the products as colorless oils.General procedure: A mixture of 2-fluorobenzoic acid (5a)(1 g, 7.13mmol) in MeOH (20 mL) was stirred for a fewminutes. Concentrated H2SO4 (1 mL) was added, and themixture was refluxed for 12 h. The reaction was monitoredby TLC using -hexane, with ethyl acetate as a developingsystem.CH2Cl2 (30 mL) was then added, and the mixture wasextracted with distilled H2O (3 × 20 mL).The organic phasewas separated, dried on anhydrous Na2SO4, and evaporatedunder vacuum to afford corresponding ester 6a in almostquantitative yield in oil form (1.09 g).

Molecular Weight:168.16
XLogP3:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:168.05865769
Monoisotopic Mass:168.05865769
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes