Diiodomethane → HCID 67404112, compound

HRID 906200Notes

Reaction equation

HRID 906200 reaction equation
N[C:2]1[C:3]([C:16]#[N:17])=[CH:4][C:5]([C:12]([F:15])([F:14])[F:13])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[I:18]CI.N(OCCC(C)C)=O>C1COCC1.[Cu]I>[C:16]([C:3]1[C:2]([I:18])=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([C:12]([F:15])([F:14])[F:13])[CH:4]=1)#[N:17]

Participants

6

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 67403359HCID 67403359, compound

Product 1

HCID 67404112HCID 67404112, compoundYield 48%

Reagents, catalysts & solvents 2

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

Procedure

Methyl 5-amino-4-cyano-2-(trifluoromethyl)benzoate (250 mg, 1.02 mmol) was dissolved in THF (6 mL), and the mixture was sparged with nitrogen for 15 minutes. Copper (I) iodide (195 mg, 1.02 mmol) and diiodomethane (0.4 mL, 4.95 mmol) were added followed by isoamyl nitrite (0.4 mL, 3.01 mmol), and the mixture was stirred at reflux for 2.5 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, was dried over sodium sulfate, then filtered and concentrated to provide a semi-solid which was purified by column chromatography (silica gel, 20-50% dichloromethane in hexanes) to afford methyl 4-cyano-5-iodo-2-(trifluoromethyl)benzoate (174 mg, 0.49 mmol, 48% yield). 1H NMR (400 MHz, CDCl3): δ 8.33 (s, 1H), 7.93 (s, 1H), 3.98 (s, 3H); GCMS for C10H5F3INO2: 355 (M+).

Workup

  1. customthe mixture was sparged with nitrogen for 15 minutes
  2. temperatureat reflux for 2.5 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, was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide a semi-solid which
  10. customwas purified by column chromatography (silica gel, 20-50% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-4a82ad133301478fbb18bb24e5341e6b
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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