The synthetic process of Ethyl 5-chloro-3-phenylindole-2-carboxylate (CAS NO. ) contains 2 steps. The synthetic route is as follows:

A. Preparation of N-(2-Benzoyl-4-chlorophenyl)oxalamic acid ethyl ester. A two-necked, round-bottomed flask (500 mL) equipped with a -coated magnetic stirring bar, a gas inlet, and a dropping funnel is purged with argon. The flask is charged with 2-amino-5-chlorobenzophenone (13.9 g, 60 mmol), dichloromethane (100 mL), and pyridine (20 mL). A solution of ethyl oxalyl chloride (9.6 g, 70.3 mmol) in dichloromethane (20 mL) is added dropwise through the addition funnel over a period of 45 min at 0°C (ice bath), and the resulting suspension is stirred for another 1.5 hr at ambient temperature. An aqueous saturated solution of sodium bicarbonate (40 mL) is added dropwise, and the biphasic system is stirred for 1.5 hr until evolution of gas ceases. The layers are separated, and the aqueous layer is extracted with dichloromethane (3 × 50 mL). The combined organic phases are washed with water (50 mL), dried (Na₂SO₄), filtered, and evaporated. The residual pyridine is removed by azeotropic distillation with toluene (3 × 100 mL) under reduced pressure on a rotary evaporator, and the residue is dried under vacuum (10^-3 mm) to afford N-(2-benzoyl-4-chlorophenyl)oxalamic acid ethyl ester (19.6 g, 98%), that is directly used in the next step.

B. Preparation of Ethyl 5-chloro-3-phenylindole-2-carboxylate. An oven-dried, two-necked, round-bottomed, 500-mL flask equipped with a Teflon-coated magnetic stirring bar, a glass stopper, and a reflux condenser connected to the argon line is flushed with argon. The flask is charged with N-(2-benzoyl-4-chlorophenyl)oxalamic acid ethyl ester (13.27 g, 40 mmol), titanium(III) chloride (TiCl₃) (12.34 g, 80 mmol), zinc dust (10.45 g, 160 mmol), and ethylene glycol (DME) (250 mL). The resulting suspension is heated at reflux for 2 hr with stirring, during which time a characteristic color change from violet (TiCl₃) to blue to black occurs. The mixture is allowed to cool to ambient temperature and then slowly filtered through a short pad of silica on a sintered glass funnel. The inorganic residues are thoroughly washed with ethyl acetate (5 × 50 mL), and the combined filtrates are concentrated to dryness on a rotary evaporator. For purification, the crude product is refluxed in toluene (120 mL), and the resulting yellow solution is decanted from the oily residues. The product crystallizes upon standing at ambient temperature. The precipitated needles are collected on a funnel, washed with cold hexane (3 × 10 mL), and dried under reduced pressure to afford a first crop of ethyl 5-chloro-3-phenylindole-2-carboxylate as pale-yellow needles (9.3-9.7 g, 78-81%). Evaporation of the filtrate and recrystallization of the residue from toluene (20 mL) as described above gives a second fraction of product (0.8-1.4 g, 7-12%).