Water → HCID 58968742, compound

HRID 2075039Notes

Reaction equation

HRID 2075039 reaction equation
[Br:1][C:2]1[CH:19]=[C:18]([CH3:20])[C:17](I)=[CH:16][C:3]=1[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15].[F-:22].[K+].COC(=O)[C:27](Cl)([F:29])[F:28].O>CN(C)C=O.[Cu](I)I.ClCCl>[Br:1][C:2]1[CH:19]=[C:18]([CH3:20])[C:17]([C:27]([F:29])([F:22])[F:28])=[CH:16][C:3]=1[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15]

Participants

8

Reactant 4

HCID 962WaterHCID 73935Methyl chlorodifluoroacetateHCID 522689Potassium FluorideHCID 58968672HCID 58968672, compound

Product 1

HCID 58968742HCID 58968742, compoundYield 64.6%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-(2-bromo-5-iodo-4-methylbenzyl) isoindoline-1,3-dione (560 mg, 1.22 mmol) in N,N-dimethylformamide (10 mL) was added copper iodide (467.6 mg, 2.45 mmol) and potassium fluoride (291.1 mg, 4.91 mmol). The solution was heated to 120° C. After 20 minutes methyl-2-chloro-2,2-difluoroacetate (709.71 mg, 4.91 mmol) was added to the orange suspension and the heating was continued for 8 hours. After about 30 minutes gas evolution was observed and the solution became yellow. After cooling the mixture was poured into water (50 mL), forming an emulsion, to which was added dichloromethane (300 mL). The mixture was stirred for 20 minutes then filtered through a pad of Celite®, rinsing through with dichloromethane. The organic layer was washed with 25 mL of 2 N HCl, dried with anhydrous sodium sulfate and concentrated under reduced pressure to a yellow solid (510 mg). This material was recrystallized from hot ethanol (30 mL) then allowed to stand at room temperature for 72 hours. The crystals were collected by filtration and rinsed with ethanol to give a white crystalline solid (314 mg). Final purification was achieved by recrystallization from hot acetonitrile to give the title compound (200 mg, 40%). 1H NMR (400 MHz, CDCl3) δ 7.86 (m, 2H) 7.74(m, 2H) 7.50 (s, 1H) 7.39(s, 1H) 4.84(s, 2H) 2.32(s, 3H). GC-MS calc. 398, found 376 (M-F)

Workup

  1. waitAfter about 30 minutes gas evolution was observed
  2. temperatureAfter cooling the mixture
  3. customforming an emulsion
  4. filtrationthen filtered through a pad of Celite®
  5. washrinsing through with dichloromethane
  6. washThe organic layer was washed with 25 mL of 2 N HCl
  7. dry with materialdried with anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure to a yellow solid (510 mg)
  9. customThis material was recrystallized from hot ethanol (30 mL)
  10. waitto stand at room temperature for 72 hours
  11. filtrationThe crystals were collected by filtration
  12. washrinsed with ethanol

Sources & evidence

ORD record
ord-ee8c8ba6ac2c420a89722d266d57647e
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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