4-Bromo-2-fluorophenylacetic acid

REFERENCE EXAMPLE 61 NaOH (56.2 mL, 112 mmol) was added to a solution of 2-(4-bromo-2-fluorophenyl)acetonitrile (4.01 g, 18.74 mmol) in MeOH (30 mL).The mixture was stirred at 100° C. for 12 h. The mixture was cooled to rt. Then the solution was concentrated and distributed between EA and saturated NaHCONaOH (56.2 mL, 112 mmol) was added to a solution of 2-(4-bromo-2-fluorophenyl)acetonitrile (4.01 g, 18.74 mmol) in Me OH (30 mL). The mixture was stirred at 100 °C for 12 h. The mixture was cooled to rt. Then the solution was concentrated and distributed between EA and saturated NaHC0Step B: 4-Bromo-2-fluoro-phenyl-acetic acid(4-Bromo-2-fluoro-phenyl)-acetonitrile (41.4 g, 174 mmol) (21.2 g, 99.1 mmol) was suspended in 30percent aq. HCI (200 ml.) and heated to reflux for 20 hours. After cooling to room temperature, the solids were collected by filtration, washed with water and allowed to dry in open air. The solids were azeotroped with toluene under reduced pressure to remove the final traces of water, yielding the title compound as a solid (21 .7 g, 89 mmol, 94percent).To a solution of 2-(4-bromo-2-fluorophenyl)acetonitrile (397 g, 1.82 mol) in MeOH (500 mL) stirred under N2 at 20 °C was added NaOH (2.22 L, 2.5M, 5.56 mol) solution in one charge. The reaction mixture was stirred at 80 °C for 5 h. Then the solution wasconcentrated and neutralized with cone. HC1 to pH = 5 with stirring. Then the solution was extracted with EA (1.5 L x 2). Another two batches were prepared following the same procedure. Then the three batches were combined. The combined organic extract was washed with brine, dried over Na2504, filtered and concentrated in vacuo to give the pure 2-(4-bromo-2-fluorophenyl)acetic acid (1200 g, 92percent): TLC (PE/EA = 5:1, Rf = 0.2); ‘HNIVIR (400 IVIFIz, CDC13) 7.24 (br. s., 1H), 7.12 (t, J 7.9 Hz, 1H), 3.65 (s, 2H).Step 5 : 2-(4-Bromo-2-fluorophenyl)acetic acid To a solution of 2-(4-bromo-2-fluorophenyl)acetonitrile (397 g, 1.82 mol) in MeOH (500 mL) stirred under NA solution of (4-bromo-2-fluorophenyl)acetonitrile (2.345g, 10.96mmol) in ethanol (60ml) and water (18ml) was treated with potassium hydroxide (5.2Og, 93mmol, 8.5 equiv) and refluxed for 5 hours. The volatiles were distilled off, the residue was diluted with water and poured into diluted cold hydrochloric acid and the precipitated solid was filtered. The desired product was dried under high vacuum at 37A solution of (4-bromo-2-fluorophenyl)acetonitrile (D29, 2.354 g, 10.9 mmol) in ethanol (60 ml) and water (18 ml) was treated with potassium hydroxide (5.2 g, 93.09 mmol) and refluxed for 5 hours. The volatiles were evaporated off under reduced pressure and the residue was diluted with water and poured into cold, dilute hydrochloric acid and the precipitated solid was filtered. The solid was dried under high vacuum at 37° C. for 48 hours (2.283 g, 89.7percent).A mixture of (4-BROMO-2-FLUOROPHENYL) ACETONITRILE (8.55 g, 40 mmol) from step 1 in Example A (97); Potassium hydroxide (11.52 g, 320 mmol) ; Ethanol (80 ml) and water (16 ml) was heated at 70 C for 24 hours. The mixture was then diluted with water (50 ML), and subsequently extracted with ether (3x 75 ML). The pH of the aqueous layer was adjusted to approximately 3 with dropwise addition of 1 N H2SO4. After the aqueous layer was extracted with ether (3X125 ml), the combined organic layers were washed with brine and dried over MgSO4. The solvent was removed to give product (4.50 g, 48percent YIELD). H NMR (CDCl3) No. : 3.60 (s, 2H), 7.07-7. 22 (m, 3H).8.1/(4-bromo-2-fluorophenyl)acetic acid; 0.09 g of lithium hydroxide monohydrate is added to 0.37 g (1.4 mmol) of ethyl ester of (4-bromo-2-fluorophenyl)acetic acid in solution in 8 ml of a solvent mixture THF/methanol/water (1/1/1), and the reaction mixture is stirred for 3 h at room temperature. The reaction mixture is acidified with 1N HCl solution, then extracted with dichloromethane (20 ml). The organic phases are combined, dried over NaOxalyl chloride (3.2 mL) and DMF (one drop) were added to a suspension of 4-bromo-2-fluorobenzoic acid (4.0 g) in CHClSynthesis of Compound 10, N-(3-fluorobenzyl)-4-phenyl-2-fluorophenylacetamide, KX1-313; Synthesis of 4-Bromo-2-fluoro-phenylacetamide: 4-Bromo-2-fluorobenzylbromide (5 gm, 18.7 mmole) was dissolved in 30 ml ethanol, to which water solution (10 ml) of KCN (2.43 gm, 37.4 mmole) was added, refluxed overnight, then it was cooled to room temperature, poured into 200 ml of crushed ice, filtered, chromatographed using 1:1 ethyl acetate followed by ethyl acetate (the cyano compound was hydrolyzed on the silica gel to produce the carboxamide), which was evaporated to produce white solid, (1.3 gm, 32percent) H

Molecular Weight:233.03
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:231.95352
Monoisotopic Mass:231.95352
Topological Polar Surface Area:37.3
Heavy Atom Count:12
Complexity:174
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes