Methyl 2,4-dichlorobenzeneacetate

clear colorless to yellow liquid

To a solution of 2, 4-dichlorophenylacetic acid (3.5 g, 17.1 mmol) in MeOH (100 mL) was added concentrated H2SO4 (20 drops). After the reaction mixture was heated at reflux overnight, the solvent was removed in vacuo. The residue was diluted with cold water and extracted with EtOAc. The combined organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4, and filtered. The solvent was removed in vacuo, and the crude product was purified by column chromatography with (4:1 hexanes/EtOAc) to give 8 (3.56 g, 95percent) as a clear oil: 1H NMR (DMSO-d6) δ 7.40 (s, 1H), 7.22 (d, J = 1.5 Hz, 2H), 3.74 (s, 2H), 3.71 (s, 3H).[0196] 2-(2, 4-Dichlorophenyl)acetic acid (1.0 g, 4.9mmol) in MeOH (20 mL) saturated with HCI gas was stirredat 60° C. for 1 hr. After the starting material was consumedcompletely detected by TLC, the solution was concentrated invacuum to get the title compound (0.9 g, 84.1 percent) as yellow oil.Reference Example-5 To a solution of 2, 4-dichlorophenylacetic acid (3.5 g, 17.1 mmol) in MeOH (100 mL) was added concentrated H2SO4 (20 drops). After the reaction mixture was heated at reflux overnight, the solvent was removed in vacuo. The residue was diluted with cold water and extracted with EtOAc. The combined organic layer was washed with saturated NaHCO3, brine, dried over Na2SO4, and filtered. The solvent was removed in vacuo, and the crude product was purified by column chromatography with (4:1 hexanes/EtOAc) to give 8 (3.56 g, 95%) as a clear oil: 1H NMR (DMSO-d6) delta 7.40 (s, 1H), 7.22 (d, J = 1.5 Hz, 2H), 3.74 (s, 2H), 3.71 (s, 3H).[0196] 2-(2, 4-Dichlorophenyl)acetic acid (1.0 g, 4.9mmol) in MeOH (20 mL) saturated with HCI gas was stirredat 60 C. for 1 hr. After the starting material was consumedcompletely detected by TLC, the solution was concentrated invacuum to get the title compound (0.9 g, 84.1 %) as yellow oil.General procedure: Isatin based Schiff bases (1-20) were synthesized in three steps, first an esterification carried out by reacting different carboxylicacid with methanol in sulphuric acid (2-3 ml) under reflux conditionfor 12-16 h. The completion of reaction was monitored byTLC. After completion of reaction, reaction mixture was extractedwith hexane to obtained pure esters. Then esters were refluxedwith hydrazine hydrate in methanol with few drops of glacial aceticacid for 3 h. After completion of reaction, reaction mixture waswashed with chloroform to obtained different hydrazides. Thesehydrazides (1mmole) each were than treated with different Isatin(1mmole) in methanol having catalytic amount of glacial acetic acidfor 2-4 h. Reaction completion was monitored through periodicTLC. After completion of reaction, reaction mixture was washedwith n-hexane to obtain our desired products (1-20). The structureof all compounds was established through EI-MS and 1H NMR.General procedure: General synthetic procedure for the key lactone intermediates II (6a-6k), for example 6a.2-(O-tolyl) acetic acid (0.15 g, 1 mmol) was dissolved in 15 mL of methanol, slowly add 2-3 drops ofconcentrated sulfuric acid, then refluxing for 8 h and monitored by TLC, after the reaction is completed, the solvent methanol was removed by rotary evaporation, 30 mL of water was added to the residueand stirred, extracted three times with ethyl acetate, washed with water, dried and concentrated to givecompound 5a. The obtained compound 5a was placed in a round bottom flask, and 1.2 eq of methylglycolate, 20 mL of tetrahydrofuran, and 2.2 eq of potassium t-butoxide were added, refluxing andstirring the reaction and monitored by TLC, after the reaction is completed, 50 mL of water was addedto the residue and stirred, adjust the pH of the solution to 5-6, then extracted three times with ethylacetate, washed with water, dried and concentrated to obtain key lactone intermediates II (6a)List of Compounds 1: ... ETHYL 3, 4-DIMETHOXYPHENYLACETATE ETHYL M-TOLYLACETATE 2, 4-DICHLOROPHENYLACETIC ACID METHYL ESTER ETHYL 4-CHLOROPHENYLACETATE ...General procedure: 1. To a solution of Compound 1 (20 g, 117.6 mmol) in MeOH (100 mL) was added SOCl2 (10 mL) dropwise at 0 C The resulting solution was stirred at reflux overnight. TLC indicated reaction completion. The solvent was removed in vacuum, and the residue was treated with water and extracted with EA. The organic extracts were washed with saturated NaHCO3 solution, brine, dried over anhydrous Na2SO4, filtered and concentrated to give Compound 2 (21 g, 97.2 %).General procedure: General synthetic procedure for the key lactone intermediates II (6a-6k), for example 6a.2-(O-tolyl) acetic acid (0.15 g, 1 mmol) was dissolved in 15 mL of methanol, slowly add 2-3 drops ofconcentrated sulfuric acid, then refluxing for 8 h and monitored by TLC, after the reaction is completed, the solvent methanol was removed by rotary evaporation, 30 mL of water was added to the residueand stirred, extracted three times with ethyl acetate, washed with water, dried and concentrated to givecompound 5a. The obtained compound 5a was placed in a round bottom flask, and 1.2 eq of methylglycolate, 20 mL of tetrahydrofuran, and 2.2 eq of potassium t-butoxide were added, refluxing andstirring the reaction and monitored by TLC, after the reaction is completed, 50 mL of water was addedto the residue and stirred, adjust the pH of the solution to 5-6, then extracted three times with ethylacetate, washed with water, dried and concentrated to obtain key lactone intermediates II (6a)

Molecular Weight:219.06
XLogP3:3.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:217.9901349
Monoisotopic Mass:217.9901349
Topological Polar Surface Area:26.3
Heavy Atom Count:13
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes