Diiodomethane → Benzoic acid, 4-cyano-2-fluoro-5-iodo-, methyl ester

HRID 906171Notes

Reaction equation

HRID 906171 reaction equation
N[C:2]1[C:3]([C:13]#[N:14])=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[I:15]CI.N(OCCC(C)C)=O.C(OCC)(=O)C>C1COCC1.[Cu]I.O>[C:13]([C:3]1[C:2]([I:15])=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:12])[CH:4]=1)#[N:14]

Participants

8

Reactant 4

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 8857Ethyl AcetateHCID 67403793Benzoic acid, 5-amino-4-cyano-2-fluoro-, methyl ester

Product 1

HCID 67404196Benzoic acid, 4-cyano-2-fluoro-5-iodo-, methyl esterYield 63%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-amino-4-cyano-2-fluorobenzoate (437 mg, 2.2 mmol) in THF (13 mL) was added copper(I) iodide (419 mg, 2.2 mmol), diiodomethane (890 uL, 11 mmol), and isoamyl nitrite (890 uL, 6.6 mmol). The solution was heated to reflux for 4 h and was then allowed to cool to room temperature. After dilution with ethyl acetate, water was added and the mixture was filtered through celite. The biphasic filtrate was partitioned. The organic phase was dried over magnesium sulfate, filtered, and concentrated. The residue was then subject to column chromatography to provide impure methyl 4-cyano-2-fluoro-5-iodobenzoate (452 mg, ˜63% purity, ˜0.93 mmol). The remainder of the material consisted primarily of methyl 4-cyano-2-fluorobenzoate and was carried forward into the subsequent reaction without further purification. 1H NMR (400 MHz, CDCl3): 8.44 (d, 1H), 7.43 (d, 1H), 3.97 (s, 3H); MS (EI) for C9H5FINO2: 305 (M+).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 4 h
  3. filtrationthe mixture was filtered through celite
  4. customThe biphasic filtrate was partitioned
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-426a2ebf764f484a88880a5cd28879d3
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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