Phenolphthalein → alpha-(2-Fluoro-4-methylphenylamino)isovaleric acid

HRID 1389349Notes

Reaction equation

HRID 1389349 reaction equation
Br[CH:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].C1C=C2C(OC(C3C=CC(O)=CC=3)(C3C=CC(O)=CC=3)C2=CC=1)=O.C[O-].[Na+].C(=O)([O-])[O-].[K+].[K+].[F:42][C:43]1[CH:49]=[C:48]([CH3:50])[CH:47]=[CH:46][C:44]=1[NH2:45].[OH-].[Na+].CCOCC>CO.CN(P(N(C)C)(N(C)C)=O)C>[F:42][C:43]1[CH:49]=[C:48]([CH3:50])[CH:47]=[CH:46][C:44]=1[NH:45][CH:2]([CH:6]([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4]

Participants

9

Reactant 6

HCID 4764PhenolphthaleinHCID 112682-Bromoisovaleric acidHCID 11430Potassium CarbonateHCID 679842-Fluoro-4-methylanilineHCID 10942334Sodium MethoxideHCID 86719931NaOH ether

Product 1

HCID 20482718alpha-(2-Fluoro-4-methylphenylamino)isovaleric acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

A solution of α-bromoisovaleric acid (8.17 mmole) in methanol is titrated to the phenophthalein end point using sodium methoxide. The solvent is removed by rotoevaporation and then there is added potassium carbonate (1.69 g), 2-fluoro-4-methylaniline (16.38 mmole) and 3 ml HMPT. The reaction is heated at 60° for about 5 hours and then worked up with 5% sodium hydroxide/ether and washed with water (3×). The basic layer is acidified and extracted with ether, washed with water and brine, dried over sodium sulfate and rotoevaporated to yield α-(2-fluoro-4-methylphenylamino)isovaleric acid. (2-Fluoro-4-methylaniline is prepared from 3-fluoro-4-nitrotoluene in a Parr bottle using platinum oxide and hydrogen in ethanol.)

Workup

  1. customThe solvent is removed by rotoevaporation
  2. temperatureThe reaction is heated at 60° for about 5 hours
  3. washwashed with water (3×)
  4. extractionextracted with ether
  5. washwashed with water and brine
  6. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-63741f86cef54bbbb0bea496a807a4d7
Source dataset
uspto-grants-1981_01
Patent number
US04243819

Reaction notes

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