Water → Phthalimide

HRID 589638Notes

Reaction equation

HRID 589638 reaction equation
[N+](C)([O-])=O.C(=O)([O-])[O-].[K+].[K+].BrC1C=C(C(=O)/C=C(\C2C=C(Cl)C=C(Cl)C=2)/C(F)(F)F)C=CC=1C[N:35]1[C:43](=[O:44])[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[C:36]1=[O:45].O>C1(C)C=CC=CC=1>[C:36]1(=[O:45])[C:37]2[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:43](=[O:44])[NH:35]1

Participants

6

Reactant 4

HCID 962WaterHCID 6375Nitromethane2×HCID 11430Potassium Carbonate2×HCID 86695996HCID 86695996, compound

Product 1

HCID 6809PhthalimideYield 344.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of anthracenylmethyl quininium bromide (200 mg), nitromethane (0.04 ml), potassium carbonate (94 mg) and 2-[[2-bromo-4-[(E)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-but-2-enoyl]phenyl]methyl]isoindoline-1,3-dione (200 mg) in toluene (2 mL) under argon, was heated for 2 hours at 50° C. then potassium carbonate (64 mg) was added. The reaction was heated for 24 hours at 50° C. then more nitromethane (0.02 mL) was added. The reaction was heated again at 50° C. for 1.5 hours then was allowed to stand at room temperature for 18 hours. Water was then added and the resulting mixture was extracted with dichloromethane and the combined organic fractions were dried over sodium sulfate. The crude product was purified by flash chromatography (0% to 25% ethyl acetate in cyclohexane) to afford 2-[[2-bromo-4-[(3R)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-nitromethyl)butanoyl]phenyl]methyl]isoindoline-1,3-dione (174 mg). Chiral HPLC analysis (Chiralpack IB, Heptane/isopropanol 70/30, flow: 1 mL, retention time 12.10 minutes (major enantiomer), 14.34 minutes (minor enantiomer) indicated that the reaction proceeded with 49% enantioselectivity in favor of the R enantiomer.

Workup

  1. temperatureThe reaction was heated again at 50° C. for 1.5 hours
  2. extractionthe resulting mixture was extracted with dichloromethane
  3. dry with materialthe combined organic fractions were dried over sodium sulfate
  4. customThe crude product was purified by flash chromatography (0% to 25% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-354e7ec7f45c4a2392ec4396634f2503
Source dataset
uspto-grants-2016_01
Patent number
US09233920B2

Reaction notes

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