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

Temperature

140 °C

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).

1. customThe solvent was removed by concentration
2. dissolutionThe residue was dissolved in MeOH (50 mL)
3. additiontreated with 4 N NaOH (5 mL) at rt for 0.5 h
4. additionThe reaction mixture was then diluted with AcOEt
5. washwashed with water and brine
6. concentrationAfter concentration the residue
7. customwas purified by flash column (5%-30% AcOEt in Hex)

ORD record

ord-1473a77e4acc4f3faf38121d732dc94a

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07553833B2