Imidazole → [1-(4-Fluoro-phenyl)-2-iodo-ethyl]-carbamic acid tert-butyl ester

HRID 539619Notes

Reaction equation

HRID 539619 reaction equation
[Cl-].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[I:22]I.N1C=CN=C1.[C:29]([O:33][C:34](=[O:46])[NH:35][CH:36]([C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1)[CH2:37]O)([CH3:32])([CH3:31])[CH3:30]>C(Cl)Cl>[C:29]([O:33][C:34](=[O:46])[NH:35][CH:36]([C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1)[CH2:37][I:22])([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 13797396Triphenylphosphane dichlorideHCID 58200246Tert-butyl [1-(4-fluorophenyl)-2-hydroxyethyl]carbamate

Product 1

HCID 58200314[1-(4-Fluoro-phenyl)-2-iodo-ethyl]-carbamic acid tert-butyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a room temperature solution of triphenylphosphine dichloride (1.53 g (5.85 mmol) in methylene chloride was added iodine (1.481 g, 5.85 mmol). The mixture was stirred for fifteen minutes, then imidazole (663 mg, 9.74 mmol) was added. The mixture was stirred another 15 minutes, then [1-(4-fluoro-phenyl)-2-hydroxy-ethyl]carbamic acid tert-butyl ester (1.0 g, 3.9 mmol) was added. The mixture was heated to reflux for two hours, then stirred at room temperature overnight. Solvent was removed under reduced pressure, and the residue was partitioned between ethyl acetate and saturated aqueous sodium thiosulfate. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was chromatographed through silica (5-10% ethyl acetate/hexanes) to give 820 mg (58%) of [1-(4-fluoro-phenyl)-2-iodo-ethyl]-carbamic acid tert-butyl ester, MP=138-139° C.

Workup

  1. stirringThe mixture was stirred another 15 minutes
  2. temperatureThe mixture was heated
  3. temperatureto reflux for two hours
  4. stirringstirred at room temperature overnight
  5. customSolvent was removed under reduced pressure
  6. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium thiosulfate
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was chromatographed through silica (5-10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4d1d6fe8d4b04a86b69a86abb67c3011
Source dataset
uspto-grants-2014_10
Patent number
US08871760B2

Reaction notes

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