Ethanol → (+/-)-[10-(4-Chlorophenyl)-1-(methylsulfinyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl]acetic acid

Participants

Reaction Conditions

Reaction Steps

To a suspension of the aniline of Step 2 (5.95 g, 20 mmol) in 13 mL of water and 8 mL of concentrated HCl at 0° was added a NaNO2 solution (1.52 g in 3 mL of water). The mixture was stirred for 15 minutes at 0° C. and was adjusted to pH 3 with the addition of NaOAc. In a separate flask, a solution of the ester of Step 1 (5.1 g, 20 mmol) in 27 mL of EtOH was treated with an aqueous solution of KOH (1.12 g in 3 mL of water). The solution was then cooled to −5° C. and the diazonium salt was added to the alkaline solution. The pH was adjusted to 5 with NaOAc and the mixture was stirred at 0° C. for 16 hours. The reaction mixture was extracted with EtOAc and the combined organic layers were dried over MgSO4 and concentrated. The residue was added slowly to a 3N HCl solution in EtOH and was stirred at 70° C. for 2 hours. EtOH was removed by evaporation and water was added. The aqueous layer was extracted with CH2Cl2 and the combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 25% EtOAc in Hexanes to provide 2.1 g of the title compound as an orange solid.

Provenance & Evidence