Carbonyl bromide → 3-Hydroxy-3-methyl-7-nitro-oxindole
Reaction equation
COC(=O)C1C(=CC=CC=1[N+:13]([O-])=O)C(O)=O.Br[C:18](Br)=[O:19].Br[CH2:22][CH:23]1[C:31]2[C:26](=[C:27]([N+:32]([O-:34])=[O:33])[CH:28]=[CH:29][CH:30]=2)C(=O)[O:24]1>CC(C)=O>[OH:24][C:23]1([CH3:22])[C:31]2[C:26](=[C:27]([N+:32]([O-:34])=[O:33])[CH:28]=[CH:29][CH:30]=2)[NH:13][C:18]1=[O:19]Participants
Procedure
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.
Sources & evidence
- ORD record
- ord-b336d655775c44e58c6d6105dbbd502f
- Source dataset
- uspto-grants-2008_01
- Patent number
- US07320992B2
Reaction notes
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