4-Iodoaniline → HCID 59426413, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-difluoromethoxy-1-ethyl-1H-indole-3-carbonitrile (516.2 mg, 1.77 mmol) and tri-isopropyl borate (532.7 mg, 2.83 mmol) in THF (15 mL) is cooled to −78° C. and treated with LDA (1.5 M mono-THF in cyclohexane, 1.43 ml, 2.04 mmol). After the addition, the acetone/dry ice bath is exchanged for ice/water bath and the solution is stirred further for 30 min. The solution is cooled to −78° C. and a solution of 4-iodoaniline (390.2 mg, 1.78 mmol) in DMF (8 mL), K2CO3 (2M, 2.7 ml, 5.31 mmol) and PdCl2dppf (67.4 mg, 0.09 mmol) are added in sequence. The mixture is degassed by three successive cycles of vacuum pumping/N2 purging and is stirred overnight (ca. 16 h), after which it is poured into 4 volumes of water, and 4 volumes of ethyl acetate are added. The phases are separated, and the aqueous phase is extracted with more ethyl acetate. The organic phases are washed by water, saturated NaCl, dried over anhydrous MgSO4, filtered and evaporated. The remaining material is purified by column chromatography, eluting with 5-15% ethyl acetate/hexanes on silica gel to yield 367.5 mg (55.0% yield) of 2-(4-aminophenyl)-6-difluoromethoxy-1-(tetrahydrofuran-2-ylmethyl)-1H-indole-3-carbonitrile as a white solid.

Provenance & Evidence