Methanol → (4-Phenylamino-benzoylamino)-acetic acid

HRID 1093591Notes

Reaction equation

HRID 1093591 reaction equation
C([O:3][C:4](=[O:22])[CH2:5][NH:6][C:7](=[O:21])[C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)C.CO.O.O[Li].O>C1COCC1>[C:15]1([NH:14][C:11]2[CH:12]=[CH:13][C:8]([C:7]([NH:6][CH2:5][C:4]([OH:22])=[O:3])=[O:21])=[CH:9][CH:10]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 66591738(4-Phenylamino-benzoylamino)-acetic acid ethyl ester

Product 1

HCID 57874498(4-Phenylamino-benzoylamino)-acetic acidYield 91.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-phenylamino-benzoic acid (3.0 g, 0.01401 mol) in DMF (10 mL), was added DIPEA (5.4 g, 0.04205 mol), HOBt (2.27 g, 0.01682 mol) and EDCI.HCl (6.69 g, 0.03504 mol) at ambient temperature. After 2 minutes amino-acetic acid ethyl ester hydrochloride (2.33 g, 0.01682 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration, washed with water followed by hexane and dried to afford 4 g (95%) of (4-phenylamino-benzoylamino)-acetic acid ethyl ester. To a stirred solution (4-phenylamino-benzoylamino)-acetic acid ethyl ester (4 g, 0.01337 mol) in a mixture of THF (15 mL), methanol (15 mL) and H2O (8 mL) was added LiOH.H2O (2.24 g, 0.0535 mol). The resulting mixture was stirred at ambient temperature for 3 hours and then concentrated. The residue was diluted with water and acidified with 10% aqueous citric acid solution. The resulting precipitate was isolated by filtration and dried to afford 3.3 g (91%) of (4-phenylamino-benzoylamino)-acetic acid.

Workup

  1. concentrationconcentrated
  2. additionThe residue was diluted with water
  3. customThe resulting precipitate was isolated by filtration
  4. customdried

Sources & evidence

ORD record
ord-19294c40602f475dbff835a77b97d6b4
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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