6-Chloroindole-2-carboxylic acid ethyl ester

General procedure: A solution of 6a-d (9.2mmol) in toluene (150mL) was treated with rhodium(II) acetate dimer (203mg, 0.46mmol) at reflux for 1-2h under nitrogen atmosphere.  The solvent was removed under reduced pressure and the residue was purified on silica gel (hexane-ethyl acetate, 25∶1—18∶1, v/v) to afford compound 7a-d in 51.7percent-58.6percent overall yield.To crude 2(29 mmol) in a mixture of ethanol and glacial acetic acid (1:1, v:v, 108 mL) at room temperature was added iron powder (14.4 g, 257 mmol) and the reaction mixture was stirred at reflux for 4 h. The mixture was filtered and evaporated to dryness to give a residue which was redistributed in dichloromethane (300 mL)/1.0 M aqueous hydrochloric acid solution (400 mL). The organic layer was separated and successively washed with a saturated aqueous sodium bicarbonate solution (300 mL), brine (300 mL) and dried (Na2SO4). Evaporation followed by crystallization (hexane-dichloromethane) gave 3 as pale off-white needles (6.12 g, 94percent over2 steps). Rf (heptane/ethyl acetate, 8/2): 0.48. Mp: 176-177 o C. 1H NMR (CD2Cl2) d 9.03 (bs, 1H), 7.64 (d, J 8.6 Hz, 1H), 7.48 (s, 1H), 7.20 (d, J 1.2 Hz, 1H), 7.14 (dd, J 8.6, 1.6 Hz, 1H), 4.41 (q4, J 7.1 Hz, 2H), 1.42 (t, J 7.1 Hz, 3H). 13C NMR (CDCl3) d 161.7 [C], 136.9 [C], 131.2 [C], 128.1 [C], 125.9 [C], 123.4 [CH], 121.8 [CH], 111.6[CH], 108.5 [CH], 61.2 [CH2], 14.3 [CH3].Step 2: A 500 ml flask was charged with toluene(110 ml) was added, (E)-ethyl 2-(2-(3-chlorophenyl)hydazano)propanoate (10.6 g, 0.044 mol). Then, polyphosphoric acid (52 g) was added thereto, The reflux reaction was allowed to proceed for 6 hours.After completion of the reaction, the reaction mixture was cooled to 50 ° C. and only the toluene layer was separated.The separated toluene layer was concentrated under reduced pressure.Then toluene (50 ml) was added to the solid formed, and the mixture was refluxed for 1 hour and then cooled to room temperature.The re-crystallized solid was then filtered to give ethyl 6-chloro-lH-indole-2-carboxylate (3.4 g, 0.015 mol, 35percent).To a suspension of potassium ethoxide (9.8 g, 117 mmol) in drydiethyl ether (96 mL) were added, at room temperature under argon, ethanol (29 mL), diethyl oxalate (20 mL, 146 mmol), and 4- chloro-2-nitrotoluene (5 g, 29 mmol) in solution in diethyl ether (50 mL). The reaction mixture turned red and stirring was continued for 15 h. The reaction mixture was poured onto cold1.0 M aqueous hydrochloric acid solution (400 mL) and the aqueous layer was extracted with ethyl acetate twice (2 x 250 mL). The combined organic layers were washed with brine and dried (Na2SO4). After evaporation, crude compound 2 was directly used in the next step without further purication. Rf (heptane/ethyl ac-etate, 8/2): 0.23. To crude 2(29 mmol) in a mixture of ethanol and glacial acetic acid (1:1, v:v, 108 mL) at room temperature was added iron powder (14.4 g, 257 mmol) and the reaction mixture was stirred at reflux for 4 h. The mixture was filtered and evaporated to dryness to give a residue which was redistributed in dichloromethane (300 mL)/1.0 M aqueous hydrochloric acid solution (400 mL). The organic layer was separated and successively washed with a saturated aqueous sodium bicarbonate solution (300 mL), brine (300 mL) and dried (Na2SO4). Evaporation followed by crystallization (hexane-dichloromethane) gave 3 as pale off-white needles (6.12 g, 94percent over2 steps). Rf (heptane/ethyl acetate, 8/2): 0.48. Mp: 176-177 o C. 1H NMR (CD2Cl2) d 9.03 (bs, 1H), 7.64 (d, J 8.6 Hz, 1H), 7.48 (s, 1H), 7.20 (d, J 1.2 Hz, 1H), 7.14 (dd, J 8.6, 1.6 Hz, 1H), 4.41 (q4, J 7.1 Hz, 2H), 1.42 (t, J 7.1 Hz, 3H). 13C NMR (CDCl3) d 161.7 [C], 136.9 [C], 131.2 [C], 128.1 [C], 125.9 [C], 123.4 [CH], 121.8 [CH], 111.6[CH], 108.5 [CH], 61.2 [CH2], 14.3 [CH3].

Molecular Weight:223.65
XLogP3:3.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:223.0400063
Monoisotopic Mass:223.0400063
Topological Polar Surface Area:42.1
Heavy Atom Count:15
Complexity:247
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes