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

HRID 1662390Notes

Reaction equation

HRID 1662390 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 59%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Procedure

To a stirred solution of 66.15C (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 66.15D (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)

Sources & evidence

ORD record
ord-054d277d179e41c4be4791956cdafbac
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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