4-Mercaptobenzoic acid → (R)-N-[2-chloro-4-(4-carboxyphenylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

HRID 1062378Notes

Reaction equation

HRID 1062378 reaction equation
[SH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[Cl:11][C:12]1[CH:17]=[C:16](I)[CH:15]=[CH:14][C:13]=1[NH:19][C:20](=[O:28])[C@:21]([OH:27])([CH3:26])[C:22]([F:25])([F:24])[F:23]>CN(C=O)C.[Cu-]=O>[Cl:11][C:12]1[CH:17]=[C:16]([S:1][C:2]2[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=2)[CH:15]=[CH:14][C:13]=1[NH:19][C:20](=[O:28])[C@:21]([OH:27])([CH3:26])[C:22]([F:23])([F:25])[F:24]

Participants

5

Reactant 2

HCID 957384-Mercaptobenzoic acid2×HCID 54268602(R)-N-(2-chloro4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

Product 1

HCID 53644641(R)-N-[2-chloro-4-(4-carboxyphenylsulphanyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamideYield 95.8%

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-mercaptobenzoic acid (0.308 g), (R)-N-(2-chloro-4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 197) (0.786 g) and copper (I) oxide (0.143 g) in DMF (5 ml) was stirred and heated under reflux for 1 hour. More 4-mercaptobenzoic acid (0.308 g) was added and heating was continued for a further 2 hours. The mixture was cooled, filtered, and the filter washed with DMF (5 ml). The filtrates were concentrated by evaporation and the residual solid was extracted with boiling ethyl acetate (2×60 ml). The extracts were absorbed onto deactivated silica (silica deactivated by treatment with 10% water) and purified by chromatography eluting with 5% methanol/ethyl acetate to give the title compound (0.803 g) as a solid. NMR: 1.63 (s, 3H), 7.31 (d, 2H), 7.5 (dd, 1H), 7.68 (d, 1H), 7.89 (d, 2H), 8.22 (d, 1H), 9.8 (brs, 1H); MS (ESP−): 418; EA: found: C, 48.2; H, 3.1; N. 3.2%; CH17H13NClF3O4S requires C, 48.6; H, 3.1; N, 3.3%.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 1 hour
  3. temperatureheating
  4. temperatureThe mixture was cooled
  5. filtrationfiltered
  6. washthe filter washed with DMF (5 ml)
  7. concentrationThe filtrates were concentrated by evaporation
  8. extractionthe residual solid was extracted with boiling ethyl acetate (2×60 ml)
  9. customThe extracts were absorbed onto deactivated silica (silica deactivated by treatment with 10% water)
  10. custompurified by chromatography
  11. washeluting with 5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-672c05bf9a8a46a9aae085bd530aaee3
Source dataset
uspto-grants-2005_11
Patent number
US06960688B2

Reaction notes

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