Potassium Iodide → (R)-N-[3-Iodo-2-chlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 1267729Notes

Reaction equation

HRID 1267729 reaction equation
[Cl:1][C:2]1[C:7](Cl)=[C:6](S(NC)(=O)=O)[CH:5]=[CH:4][C:3]=1[NH:14][C:15](=[O:23])[C@:16]([OH:22])([CH3:21])[C:17]([F:20])([F:19])[F:18].N([O-])=O.[Na+].[I-:28].[K+].CCOC(C)=O>S(=O)(=O)(O)O.O>[I:28][C:7]1[C:2]([Cl:1])=[C:3]([NH:14][C:15](=[O:23])[C@:16]([OH:22])([CH3:21])[C:17]([F:20])([F:19])[F:18])[CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 8857Ethyl AcetateHCID 9843614(R)-N-[2,3-Dichloro-4-(methylaminosulphonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamideHCID 23668193Sodium Nitrite

Product 1

HCID 69539506(R)-N-[3-Iodo-2-chlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 108.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 1118Sulfuric AcidSolvent

Procedure

To a cooled solution of (R)-N-[3-amino-2-chlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Method 8) (12.5 g) in concentrated sulphuric acid (25 ml) and water (70 ml) was added a solution of sodium nitrite (3.15 g) in water (70 ml) dropwise. The reaction mixture was allowed to stir for 10 minutes and for 1 hour at ambient temperature. A solution of potassium iodide (22.2 g) in water (70 ml) was added cautiously and the mixture was heated to 100° C. for 2.5 hours. The reaction mixture was allowed to cool to ambient temperature, EtOAc (500 ml) was added and the organic phase was washed with brine (300 ml) and dried. Volatile material was removed by evaporation and the residue was purified by flash column chromatography eluting with 5-20% EtOAc/isohexane to give the title compound (13.5 g) as a cream solid. NMR (CDCl3) 1.76 (s, 3H), 3.63 (s, 1H), 7.05 (t, 1H), 7.68 (d, 1H), 8.36 (d, 1H), 8.97 (brs, 1H); m/z: 392.

Workup

  1. temperaturethe mixture was heated to 100° C. for 2.5 hours
  2. temperatureto cool to ambient temperature
  3. washthe organic phase was washed with brine (300 ml)
  4. customdried
  5. customVolatile material was removed by evaporation
  6. customthe residue was purified by flash column chromatography
  7. washeluting with 5-20% EtOAc/isohexane

Sources & evidence

ORD record
ord-6c34e3bddbb746b68f483eec6c788e0f
Source dataset
uspto-grants-2003_04
Patent number
US06552225B1

Reaction notes

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