Z-6-chloro-3-(3-chloro-benzylidene)-1,3-dihydro-indol-2-one → 6-ethoxy-spiro[cyclohexane-1,3'-[3H]indole]-2',4(1'H)-dione

Participants

Reaction Conditions

Reaction Steps

To a suspension of E/Z-6-chloro-3-(3-chloro-benzylidene)-1,3-dihydro-indol-2-one (1.45 g, 15.0 mmol) in toluene (20 mL) in a sealed tube was added (3-ethoxy-1-methylene-allyloxy)-trimethyl-silane (1.24 g, 7.5 mmol). The reaction mixture was allowed to stir at 140° C. for 16 hrs. The solvent was removed by concentration. The residue was dissolved in MeOH (50 mL) and treated with 4 N NaOH (5 mL) at rt for 0.5 h. The reaction mixture was then diluted with AcOEt and washed with water and brine. After concentration the residue was purified by flash column (5%-30% AcOEt in Hex) to give a mixture (1.2 g) of rac-(1R,2R)-6′-chloro-2-(3-chlorophenyl)spiro[5-cyclohexene-1,3′-[3H]indole]-2′,4(1′H)-dione and rac-(1R,2S,6R)-6′-chloro-2-3-chlorophenyl)-6-ethoxy-spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione (0.46 g, 18.6%) as white amorphous which was used for next steps without further purification. A small amount mixture was separated by normal phase HPLC gave rac-(1R,2S,6R)-6′-chloro-2-(3-chlorophenyl)-6-ethoxy-spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione. MS+:358 (M+1).

Provenance & Evidence