Carbonyl bromide → 3-Hydroxy-3-methyl-7-nitro-oxindole

Participants

Reaction Steps

3-Substituted oxindoles can be prepared from 7-nitrophthalic anhydride 21, for example, which can be reacted with MeOH to give the 3-nitro-phthalic acid-2-methyl ester 22 by known procedures. The 3-nitro-phthalic acid-2-methyl ester 22 is converted to the corresponding acid chloride 23 then reacted with a methyl Grignard reagent to afford the methyl-ketone 24. The methyl-ketone 24 can be converted to the bromo-ketone 25 and cyclized to the 3-bromomethyl-7-nitro-3H-isobenzofuran-1-one 26 which can be reacted with an amine to afford the 3-hydroxy-3-methyl-7-nitro-oxindole 27. The 3-hydroxy-3-methyl-7-nitro-oxindole 27 can be reduced to the corresponding 7-amino-3-hydroxy-3-methyl-oxindole 28 which can then be alkylated by reductive amination to give compound 29. Alternatively, the 3-hydroxy-3-methyl-7-nitro-oxindole 27 can be reduced to the 7-amino-3-methyl-oxindole 30 under standard hydrogenation conditions and alkylated by reductive amination to give compound 31.

Provenance & Evidence