Diiodomethane → Methyl 4-iodo-2-(trifluoromethyl)benzoate

HRID 906193Notes

Reaction equation

HRID 906193 reaction equation
N[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:12]([F:15])([F:14])[F:13])[CH:3]=1.[I:16]CI.N(OCCC(C)C)=O>C1COCC1.[Cu]I>[I:16][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:12]([F:15])([F:14])[F:13])[CH:3]=1

Participants

6

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 46311081Methyl 4-amino-2-(trifluoromethyl)benzoate

Product 1

HCID 17733366Methyl 4-iodo-2-(trifluoromethyl)benzoateYield 75%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 4-amino-2-(trifluoromethyl)benzoate (˜22 mmol), was dissolved in THF (100 mL) and the mixture was sparged with nitrogen for 15 minutes. Copper (I) iodide (4.14 g, 21.8 mmol) and diiodomethane (8.8 mL, 109 mmol) were added followed by isoamyl nitrite (8.8 mL, 66.2 mmol) and the mixture was stirred at reflux for 4 h. The mixture was cooled to ambient temperature and then was partitioned between ethyl acetate and 1N hydrochloric acid. The aqueous portion was extracted with ethyl acetate (2×). The combined organic portion was washed sequentially with 1:1 saturated sodium bicarbonate solution: 1 M sodium thiosulfate (2×) and brine, dried over sodium sulfate, then filtered and concentrated to provide a brown oil which was purified by column chromatography (silica gel, 2-40% dichloromethane in hexanes) to afford methyl 4-iodo-2-(trifluoromethyl)benzoate (5.42 g, 16.4 mmol, ˜75% yield over 2 steps) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.97 (dd, 1H), 7.52 (d, 1H), 3.93 (s, 3H); GCMS for C9H6F3IO2: 330 (M+).

Workup

  1. customthe mixture was sparged with nitrogen for 15 minutes
  2. temperatureat reflux for 4 h
  3. customwas partitioned between ethyl acetate and 1N hydrochloric acid
  4. extractionThe aqueous portion was extracted with ethyl acetate (2×)
  5. washThe combined organic portion was washed sequentially with 1:1 saturated sodium bicarbonate solution
  6. dry with material1 M sodium thiosulfate (2×) and brine, dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide a brown oil which
  10. customwas purified by column chromatography (silica gel, 2-40% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-1ae66d5cafed469588211c67c778d8d4
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

Loading…