Aniline → 3-(Phenylamino)butanoic acid

HRID 2121811Notes

Reaction equation

HRID 2121811 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:8]([OH:13])(=[O:12])/[CH:9]=[CH:10]/[CH3:11]>C1(C)C=CC=CC=1>[C:2]1([NH:1][CH:10]([CH3:11])[CH2:9][C:8]([OH:13])=[O:12])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6115AnilineHCID 637090Crotonic Acid

Product 1

HCID 117152833-(Phenylamino)butanoic acidYield 61%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of aniline (3.0 g, 32 mmol) and crotonic acid (2.0 g, 23 mmol) in toluene (20 mL) was heated at reflux for 18 h. Removal of solvent and chromatography (silica gel, EtOAc/hexane, 9/1) of the crude material afforded 2.5 g (61%) of 3-phenylaminobutanoic acid. The acid was treated with PPA (20 mL) at 110° C. for 6 h and the reaction mixture was poured into ice water (50 mL) and then was neutralized with Na2CO3 to pH 7. Extraction with EtOAc (3×60 mL) followed by chromatography (silica gel, EtOAc/hexane, 4/6) afforded 1.0 g (44%) of 1,2,3,4-tetrahydro-2-methyl-4-quinolinone (structure 59A of Scheme XLVIII, where R1═R3═H, R2═methyl) as a yellow solid. The quinolinone was treated with di-tert-butyl dicarbonate (2.2 g, 10 mmol) and DMAP (0.84 g, 6.8 mmol) in THF (15 mL) for 16 h followed by chromatography (silica gel, EtOAc/hexane, 2/8) to afford 1.1 g (68%) of 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2-methyl-4-quinolinone as a yellow oil. Data for 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2-methyl-4-quinolinone: 1H NMR (400 MHz, CDCl3) 7.99 (d, J=7.5, 1H), 7.78 (d, J=7.5, 1H), 7.50 (t, J=7.5, 1H), 7.12 (t, J=7.5, 1H), 5.10 (m, 1H), 3.04 (dd, J=17.3, 5.8, 1H), 2.57 (dd, J=17.3, 1.7, 1H), 1.56 (s, 9H), 1.22 (d, J=6.9, 3H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 h
  3. customRemoval of solvent and chromatography (silica gel, EtOAc/hexane, 9/1) of the crude material

Sources & evidence

ORD record
ord-73bd2c20d6f4497bb82fd8c0c9004e51
Source dataset
uspto-grants-2004_02
Patent number
US06696459B1

Reaction notes

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