ETHYL2-(2-CHLOROPHENYL)ACETATE

o-Chlorotoluene (1.89 g), ethanol (46 mg), di-tert-butyl peroxide (73 mg, 1 equivalent), and Pd(Xantphos)ClIntermediate AR(1)ethyl 2-(2-chlorophenyl)acetateA mixture of 2-(2-chlorophenyl)acetic acid (10 g, 58.6 mmol) in EtOH (Volume: 152 ml) was treated with H2S04 (1.719 ml, 32.2 mmol). The result mixture was refluxed overnight. The heat was removed, and the reaction mixture was concentrated. The resulting oil was dissolved in EtOAc and CAREFULLY treated with aqueous Na2C03 (3.47 g, 32.8 mmol) (CAUTION: Gas evolution) until the solution remained basic and no further gas evolution was seen. The EtOAc layer was then removed and the aqueous layer was again extracted two times with EtOAc. The combined organic layers were then washed with brine, dried over Na2S04 and concentrated in vacuo to obtain ethyl 2-(2- chlorophenyl)acetate (1 1.32 g, 57.0 mmol, 97 percent yield). LC-MS (M+H)General procedure: General Procedure A: Cu(OTf)2 (54.3 mg, 0.150 mmol, 0.30 equiv.) and arylboronic ester (1.00 mmol, 1.20 to 2.00 equiv.) were added sequentially to a 1 dram vial charged with a stirbar. The carboxylic acid (0.500 mmol, 1.00 equiv.) was added as a solution in anhydrous DMA (0.6 mL). Additional DMA (2×0.3 mL) was used to quantitatively transfer the solution to the reaction mixture. The solution was stirred until a homogeneous pale blue solution was formed (approximately 2 minutes, partially heterogeneous mixtures obtained when using increased Cu loadings), followed by the addition of triethylamine (0.42 mL, 3.0 mmol, 6.0 equiv.). The vial was sealed with a PTFE-lined cap, exposed to air via a needle, and gently stirred at room temperature. Upon completion of the reaction (24 to 72 h), the reaction mixture was diluted with EtOAc (40 mL), and washed sequentially with NH4Cl (15 mL), 0.5 M NaOH (2×20 mL), and brine (15 mL). The organic layer was dried with Na2SO4, concentrated in vacuo, and purified by silica gel chromatography. No difference was observed if reactions were prepared in an atmosphere-controlled glovebox, then exposed to ambient air.General procedure: To a cooled (0 °C) solution of Scheme 46 compound 5 (700 mg, 3.4 mmol) in dry EtOH (10 mL) was added SOCl2 (3 eq.) dropwise and the reaction mixture was stirred at 90 °C for 5 h. The reaction mixture was then concentrated, neutralized with aqueous NaHC03 and extracted with EtOAc (100 mL). The organic layer was washed with water (20 mL) and brine (20 mL), dried over Na2S04 and concentrated to give a residue which was purified by flash chromatography on silica gel (eluting with petroleum ether/EtOAc 100/0 gradually increasing to 50/50) to give Scheme 46 compound 6 (680 mg, 85.5percent) as a colorless liquid. 1H NMR (400 MHz, DMSO-d6): delta 7.66-7.56 (m, 1H), 7.25-7.13 (m, 1H), 4.10 (qd, J= 7.2, 1.6 Hz, 2H), 3.78 (d, J= 2.0 Hz, 2H), 1.17 (td, J= 7.2, 1.5 Hz, 3H). MS [ESI, MH+] = 235.4

Molecular Weight:198.64
XLogP3:2.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:198.0447573
Monoisotopic Mass:198.0447573
Topological Polar Surface Area:26.3
Heavy Atom Count:13
Complexity:170
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes