2-Fluorothiophenol → (R)-N-[2-Chloro-4-(2-fluorophenylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 1062370Notes

Reaction equation

HRID 1062370 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:18])[C@:11]([OH:17])([CH3:16])[C:12]([F:15])([F:14])[F:13].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[SH:26].C[O-].[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([S:26][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[F:19])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:18])[C@:11]([OH:17])([CH3:16])[C:12]([F:15])([F:14])[F:13]

Participants

6

Reactant 3

HCID 5202162-FluorothiophenolHCID 10942334Sodium MethoxideHCID 54268602(R)-N-(2-chloro4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

Product 1

HCID 54103294(R)-N-[2-Chloro-4-(2-fluorophenylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

Tetrakis(triphenylphosphine)palladium(0) (0.147 g) was added to a deoxygenated mixture of (R)-N-(2-chloro-4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 197) (1.0 g), 2-fluorothiophenol (0.263 ml) and sodium methoxide (0.288 g) in ethanol (50 ml). The mixture was then further deoxygenated by evacuation and refilling with argon (3 cycles), and then heated under reflux with stirring under argon for 18 hours. The mixture was treated with a further portion of tetrakis(triphenylphosphine)palladium(0) (0.147 g), heated for a further 24 hours then cooled and filtered. Volatile material was removed by evaporation and the residue was purified by flash chromatography eluting with 20% ethyl acetate/hexane to give the title compound (0.906 g) as an oil. NMR (CDCl3): 1.75 (s, 3H), 3.58 (s, 1H), 7.1 (t, 2H), 7.2-7.35 (m, 3H), 7.37 (d, 1H), 8.3 (d, 1H), 8.82 (brs, 1H); MS (ESP−): 392.

Workup

  1. customThe mixture was then further deoxygenated by evacuation and refilling with argon (3 cycles)
  2. temperatureheated
  3. temperatureunder reflux
  4. additionThe mixture was treated with a further portion of tetrakis(triphenylphosphine)palladium(0) (0.147 g)
  5. temperatureheated for a further 24 hours
  6. temperaturethen cooled
  7. filtrationfiltered
  8. customVolatile material was removed by evaporation
  9. customthe residue was purified by flash chromatography
  10. washeluting with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-f7a153da70b843139bab69fc2f6c24b8
Source dataset
uspto-grants-2005_11
Patent number
US06960688B2

Reaction notes

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