Ethyl 2-(4-bromophenyl)acetate

Clear colorless to pale yellow liquid

Preparation of Intermediate 1-bromo-4-(2-methoxy-2-methylDroDyl)benzene (1AG-1); 2-(4-Bromophenyl)acetic acid (75g, 340mmol) suspended in ethanol (341 mL) . Concentrated sulfuric acid (0.682mL, 12.79mmol) was added and reaction heated to reflux for 24 hours. Reaction concentrated and residue diluted with diethyl ether and saturation sodium bicarobonate. Layers carefully separated and organic was washed with brine, dried over sodium sulfate, filtered and concentrated to give ethyl 2-(4- bromophenyl)acetate (80.2g, 97percent) as off-white solid.Step 1: To a solution of 2-(4-bromophenyl)acetic acid (3 g, 13.95 mmol) in ethanol was slowly added sulfuric acid (0.3 mL, cat.) at room temperature. Step 1 : To a solution of 2-(4-bromophenyl)acetic acid (3 g, 13.95 mmol) in ethanol was slowly added sulfuric acid (0.3 ml_, cat.) at room temperature. The reaction mixture was heated to 100 °C for overnight. TLC showed complete consumption of starting material. The reaction mixture was cooled to room temperature and neutralized with NaHC02-(4-bromophenyl)acetic acid (15 g, 69.8 mmol) was added to ethanol (125 mL). Then, sulfuric acid (0.186 mL, 3.49 mmol) was added to the reaction and the reaction was heated to 80° C for 12 h. The reaction was confirmed complete based on TLC. Solid NaHCOStep 0 (Intermediate A): see example 85.[0556]Step 1: To a stirred solution of 2-(4-bromophenyl)acetic acid (2 g, 9.3 mmol) in ethanol (10 mL) were added sulfuric acid (0.3 mL). The reaction mixture was refluxed for overnight and cooled to room temperature. The solvent was evaporated. The residue was dissolved with ethylacetate and neutralized with NaHCOStep 1 : To a stirred solution of 2-(4-bromophenyl)acetic acid (2 g, 9.3 mmol) in ethanol (10 mL) were added sulfuric acid (0.3 mL). The reaction mixture was refluxed for overnight and cooled to room temperature. The solvent was evaporated. The residue was dissolved with ethylacetate and neutralized with NaHC0A solution of 63 grams (0.29 mole) of 4-bromophenyl acetic acid and 50 milliliters of concentrated sulfuric acid in 500 milliliters of absolute ethanol was refluxed for 8 hours then allowed to stand overnight. 4-Bromophenylacetic acid, 7-c, (30 g, 0.14 mol) was dissolved in ethanol (150 mL) at reflux along with p-toluenesulphonic acid (2.4 g, 0.014mol). The reaction mixture was then stirred overnight. The ethanol was the removed in vacuo and the residue was taken up in EA. Combined organic layers were washed with water and the aqueous layer was re-extracted with EA. Combined organic layers were then dried over Na2S04 and concentrated to afford the titled compound, 12-a, (25 g, 74percent).1H NMR (300 MHz, CDCI3) δ 1.23-1.29 (m, 3H), 3.56 (s, 2H), 4.11-4.18 (m, 2H), 7.16 (d, J=8.1 Hz, 2H), 7.44 (d, J=8.1 Hz, 2H). LC-MS (M+H)Step A: Ethyl 2-(4-bromophenyl)acetate (12-a 4-Bromophenylacetic acid, 7-c, (30 g, 0.14 mol) was dissolved in ethanol (150 mL) at reflux along with p-toluenesulphonic acid (2.4 g, 0.014mol). The reaction mixture was then stirred overnight. The ethanol was the removed in vacuo and the residue was taken up in EA. Combined organic layers were washed with water and the aqueous layer was re-extracted with EA. Combined organic layers were then dried over Na2S04 and concentrated to afford the titled compound, 12-a, (25 g, 74percent).1H NMR (300 MHz, CDCI3) δ 1.23-1.29 (m, 3H), 3.56 (s, 2H), 4.1 1-4.18 (m, 2H), 7.16 (d, J=8.1 Hz, 2H), 7.44 (d, J=8.1 Hz, 2H). LC-MS (M+H)To an ice cooled solution of 2-(3-bromophenyl)acetic acid (2.5 g, 11.62 mmol) in EtOH (25 mL), thionyl chloride (1.6 mL, 23.24 mmol) was added dropwise. The reaction mixture was heated at 80° C. for 15 h. The reaction was monitored by TLC and after completion of the reaction, the reaction mixture was concentrated under vacuum and water was added to the residue. A saturated aqueous solution of NaHCOp-Bromotoluene (2.72 g), ethanol (46 mg), di-tert-butyl peroxide (73 mg, 1 equivalent), and Pd(Xantphos)ClGeneral procedure: To a 20 mL vial with a stir bar was added aryl halide 1 (2.00 mmol), Pd(dba)(1) General procedure: Carboxylic acid (0.5 mmol) and MImC (2a, 1.0 mmol) were placed in a dry 20 mL vial with a Teflon tape-coated thread. A magnetic stirbar was added, followed by dry MeCN (1.0 mL), and the vial was quickly sealed with a plastic cap (gas is evolved during the course of the reaction. All experiments should be performed behind a blast shield if a sealed container is used.). The reaction mixture was then stirred at 23 °C for 15 min and then heated to 80 °C using a heating block for 24 h. The mixture was cooled to room temperature and then the vial was carefully opened (CAUTION: vial under pressure.). The volatiles were removed in vacuo, the resulting residue was dissolved in diethyl ether (20 mL), and then washed with 1 M HCl (10 mL). The aqueous layer was back-extracted with diethyl ether (20 mL) and the organic fractions were combined, washed with a saturated solution of NaHCOGeneral procedure: A mixture of aryl iodide (5 mmol), ethyl acetoacetate(7.5 mmol), Cu2+/4A (0.5 g, 0.1 mol percent copper) and Cs2CO3 (12.5 mmol) indioxane (10 ml) was stirred at 100 C for 12 h. The solid was filtered and thefiltrate was evaporated in vacuo. The products were purified by columnchromatography (silica gel, hexane/acetone 4:1 eluent). The products werecharacterized by 1H NMR and GC–MS.A. A.

Molecular Weight:243.10
XLogP3:3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:241.99424
Monoisotopic Mass:241.99424
Topological Polar Surface Area:26.3
Heavy Atom Count:13
Complexity:162
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes