Phenolphthalein → N-[4-(trifluoromethyl)phenyl]-D-valine

HRID 443463Notes

Reaction equation

HRID 443463 reaction equation
Br[C@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].[OH-].[K+].C1C=CC2C(C3C=CC(O)=CC=3)(C3C=CC(O)=CC=3)OC(=O)C=2C=1.[F:35][C:36]([F:45])([F:44])[C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1>CO>[F:35][C:36]([F:44])([F:45])[C:37]1[CH:38]=[CH:39][C:40]([NH:41][C@H:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4])=[CH:42][CH:43]=1

Participants

6

Reactant 4

HCID 4764PhenolphthaleinHCID 99644-(Trifluoromethyl)anilineHCID 14797Potassium HydroxideHCID 156968alpha-Bromoisovaleric acid, (R)-

Product 1

HCID 13388455N-[4-(trifluoromethyl)phenyl]-D-valine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of 10.01 g (55.3 mmol) of (R)-2-bromo-3-methylbutanoic acid in methanol is titrated with 1 M potassium hydroxide (~53 ml) in methanol to the phenolphthalein endpoint. The methanol is then removed under high vacuum at 35°, and the solid is kept at 35° under high vacuum for one hour. 4-Trifluoromethylaniline (23.89 g, 148.3 mmol) is added to the salt, and the mixture is heated in a pre-heated oil bath (90°) under nitrogen for 30 minutes. The mixture is then cooled and worked up immediately by partitioning between pentane/5% sodium hydroxide. The layers are separated and the pentane phase is extracted with 5% sodium hydroxide (2×). The combined aqueous phases are extracted with pentane (2×) and acidified with cold conc. hydrochloric acid. The aqueous phase is then extracted with ether (3×), and the combined ether phases are washed with brine and dried over magnesium sulfate. Filtration and evaporation yield (R)-2-(4-trifluoromethylphenylamino)-3-methylbutanoic acid.

Workup

  1. customThe methanol is then removed under high vacuum at 35°
  2. temperaturethe mixture is heated in a pre-heated oil bath (90°) under nitrogen for 30 minutes
  3. temperatureThe mixture is then cooled
  4. customby partitioning between pentane/5% sodium hydroxide
  5. customThe layers are separated
  6. extractionthe pentane phase is extracted with 5% sodium hydroxide (2×)
  7. extractionThe combined aqueous phases are extracted with pentane (2×)
  8. extractionThe aqueous phase is then extracted with ether (3×)
  9. washthe combined ether phases are washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationFiltration and evaporation

Sources & evidence

ORD record
ord-f0b7348b1f0e463da25ec0e4ebb09e6d
Source dataset
uspto-grants-1981_04
Patent number
US04260633

Reaction notes

Loading…