Iodine → HCID 57800179, compound

HRID 913431Notes

Reaction equation

HRID 913431 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][C:3]=1[C:15]([F:18])([F:17])[F:16].[Li]CCCC.[I:24]I>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:12])[CH3:13])=[C:4]([I:24])[C:3]=1[C:15]([F:16])([F:17])[F:18]

Participants

5

Reactant 3

HCID 807IodineHCID 715673N-[4-chloro-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamideHCID 178418339Butyllithium

Product 1

HCID 57800179HCID 57800179, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A THF (20 mL) solution of known N-[4-chloro-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide (1.49 g, 5.34 mmol) at ca. −5° C. was treated with n-BuLi (2.5 M, 5.33 mL). After 30 min, the reaction was treated with I2 (2.03 g, 8.01 mmol) dissolved in THF (3 mL). The resulting mixture was then quenched with sat. aqueous NH4Cl after 10 min. Excess I2 was removed with 10% aqueous sodium metabisulfite. The mixture was diluted with EtOAc (20 mL) and H2O (20 mL) and partitioned. The aqueous portion was extracted with EtOAc (20 mL). The combined organic portions were washed with H2O followed by brine. Drying (Na2SO4) was followed by filtration and concentration. 1H NMR of the crude mixture showed a 3.7:1 ratio of the desired (2-iodo) to the undesired regioisomer. Column chromatography (SiO2; hexanes/EtOAc) provided the title compound as a white solid (1.34 g, 62%): 1H NMR (CDCl3) δ 8.33 (d, J=6.0 Hz, 1H), 8.16 (bs, 1H), 7.49 (d, J=6.0 Hz, 1H), 1.38 (s, 9H).

Workup

  1. customThe resulting mixture was then quenched with sat. aqueous NH4Cl after 10 min
  2. customExcess I2 was removed with 10% aqueous sodium metabisulfite
  3. additionThe mixture was diluted with EtOAc (20 mL) and H2O (20 mL)
  4. custompartitioned
  5. extractionThe aqueous portion was extracted with EtOAc (20 mL)
  6. washThe combined organic portions were washed with H2O
  7. dry with materialDrying (Na2SO4)
  8. filtrationwas followed by filtration and concentration

Sources & evidence

ORD record
ord-6cfa64362aa744b6bb1c7c8e5d76ca1c
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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