Sulfuric Acid → Methyl 2'-fluoro-2-iodo-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

HRID 2098922Notes

Reaction equation

HRID 2098922 reaction equation
N[C:2]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[F:20].COCCOC.S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:36].[Na+]>O>[F:20][C:13]1[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:12]=1[C:3]1[CH:4]=[CH:5][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:7][C:2]=1[I:36]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 5238Sodium IodideHCID 80711,2-DimethoxyethaneHCID 23668193Sodium NitriteHCID 57705693Methyl 2-amino-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

Product 1

HCID 57705628Methyl 2'-fluoro-2-iodo-5'-(methyloxy)-1,1'-biphenyl-4-carboxylateYield 58%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Procedure

To a stirred solution of T10.3 (1.00 g, 3.6 mmol) in DME (10.00 mL, 96 mmol) at 23° C. was added sulfuric acid (0.19 mL, 3.6 mmol) in water (8 mL), followed by dropwise addition of a solution of sodium nitrite (0.38 g, 5.4 mmol) in water (2 mL) at 0° C. over 30 minutes. The reaction was then stirred for 20 minutes. To the mixture was added a solution of sodium iodide (3.0 g, 20 mmol) in water (7 mL) at 0° C. The resulting mixture was then stirred for 1 hour. The reaction was quenched with sodium thiosulfate and extracted three times with diethyl ether. After drying over anhydrous magnesium sulfate and filtering, the organic solvent was removed under reduced pressure and the product was purified on silica gel (0-40% EtOAc in hexanes) to yield a colorless solid T10.4 (0.820 g, 58% yield).

Workup

  1. stirringThe resulting mixture was then stirred for 1 hour
  2. customThe reaction was quenched with sodium thiosulfate
  3. extractionextracted three times with diethyl ether
  4. dry with materialAfter drying over anhydrous magnesium sulfate
  5. filtrationfiltering
  6. customthe organic solvent was removed under reduced pressure
  7. customthe product was purified on silica gel (0-40% EtOAc in hexanes)
  8. customto yield a colorless solid T10.4 (0.820 g, 58% yield)

Sources & evidence

ORD record
ord-8e1fc97de3e34456a3ac934e9cd43558
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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