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

HRID 2120360Notes

Reaction equation

HRID 2120360 reaction equation
N[C:2]1[C:3]([Cl:18])=[C:4]([NH:8][C:9](=[O:17])[C@:10]([OH:16])([CH3:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.N([O-])=O.[Na+].[I-:23].[K+].CCOC(C)=O>S(=O)(=O)(O)O.O>[I:23][C:2]1[C:3]([Cl:18])=[C:4]([NH:8][C:9](=[O:17])[C@:10]([OH:16])([CH3:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 8857Ethyl AcetateHCID 23668193Sodium NitriteHCID 58964770(R)-N-[3-Amino-2-chlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

Product 1

HCID 69539506(R)-N-[3-Iodo-2-chlorophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 77.6%

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 32) (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-5b3d90078a244a7bb5da8cf099362c89
Source dataset
uspto-grants-2004_02
Patent number
US06689909B1

Reaction notes

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