Hexane → 1-(2-Diethylaminoethyl)-4-trifluoromethyl-6-iodo-3-hydroxy-3-(2,4-difluorophenyl)oxindole
Reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[F:9].[Li]CCCC.CCCCCC.[CH2:21]([N:23]([CH2:42][CH3:43])[CH2:24][CH2:25][N:26]1[C:36]2[C:31](=[C:32]([C:38]([F:41])([F:40])[F:39])[CH:33]=[C:34]([I:37])[CH:35]=2)[C:29](=[O:30])[C:27]1=[O:28])[CH3:22]>C1COCC1>[CH2:42]([N:23]([CH2:21][CH3:22])[CH2:24][CH2:25][N:26]1[C:36]2[C:31](=[C:32]([C:38]([F:39])([F:41])[F:40])[CH:33]=[C:34]([I:37])[CH:35]=2)[C:29]([OH:30])([C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=2[F:9])[C:27]1=[O:28])[CH3:43]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 1-bromo-2,4-difluorobenzene (0.13 mL, 1.15 mmol) in THF (7.5 mL) was added dropwise 1.47 N BuLi in hexane (0.77 mL, 1.13 mmol) at −78° C. and the mixture was stirred for 15 min. To the resulting solution was added dropwise a solution of 1-(2-diethylaminoethyl)-4-trifluoromethyl-6-iodoisatin (500 mg, 1.14 mmol) in THF (6 mL) over 15 min at −78° C. The mixture was stirred for 40 min at the same temperature and the reaction was quenched with aqueous NaHCO3. The mixture was extracted with ethyl acetate and the extracts were dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography with 80:1 to 50:1 chloroform/methanol to give the title compound (576 mg, 91%).
Workup
- stirringThe mixture was stirred for 40 min at the same temperature
- customthe reaction was quenched with aqueous NaHCO3
- extractionThe mixture was extracted with ethyl acetate
- dry with materialthe extracts were dried over MgSO4
- concentrationconcentrated
- customThe residue was purified by silica gel column chromatography with 80:1 to 50:1 chloroform/methanol
Sources & evidence
- ORD record
- ord-4fcf88a7d5514c4ba35a2a282486b947
- Source dataset
- uspto-grants-2003_06
- Patent number
- US06576656B1
Reaction notes
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