Lithium hydroxide, monohydrate → (2S)-2-[[2,6-dichloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-[(3,5-dihydroxybenzoyl)amino]propanoic acid

HRID 393095Notes

Reaction equation

HRID 393095 reaction equation
O.[OH-].[Li+].[Cl:4][C:5]1[CH:30]=[C:29]([C:31]([NH:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([OH:41])[CH:36]=2)=[O:32])[CH:28]=[C:27]([Cl:42])[C:6]=1[C:7]([NH:9][C@H:10]([C:23]([O:25]C)=[O:24])[CH2:11][NH:12][C:13](=[O:22])[C:14]1[CH:19]=[C:18]([OH:20])[CH:17]=[C:16]([OH:21])[CH:15]=1)=[O:8]>O.O1CCCC1.CO>[Cl:4][C:5]1[CH:30]=[C:29]([C:31]([NH:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([OH:41])[CH:36]=2)=[O:32])[CH:28]=[C:27]([Cl:42])[C:6]=1[C:7]([NH:9][C@H:10]([C:23]([OH:25])=[O:24])[CH2:11][NH:12][C:13](=[O:22])[C:14]1[CH:15]=[C:16]([OH:21])[CH:17]=[C:18]([OH:20])[CH:19]=1)=[O:8]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 131723045N-[2,6-dichloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dihydroxybenzoylamino)-L-alanine, methyl ester

Product 1

HCID 9872589(2S)-2-[[2,6-dichloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-[(3,5-dihydroxybenzoyl)amino]propanoic acidYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of lithium hydroxide monohydrate (160 mg, 3.8 mmol) in water (10 mL) was added to a solution of N-[2,6-dichloro-4-[[[(3-hydroxyphenyl)methyl]amino]-carbonyl]benzoyl]-3-(3,5-dihydroxybenzoylamino)-L-alanine, methyl ester (490 mg, 0.85 mmol) in tetrahydrofuran/methanol (3:1; 40 mL). The solution was stirred at room temperature overnight and then the solvent was evaporated. Tetrahydrofuran and water (75 mL each) were added followed by 1 M HCl (10 mL). The cloudy white solution was heated at approx. 50° C. for 10 min and then allowed to stand overnight at room temperature. The solvents were evaporated and the residue was dissolved in methanol/water (1:4; 60 mL) and purified by HPLC in 10 mL portions. Fractions homogeneous for the product were pooled and lyophilized to give N-[2,6-dichloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dihydroxybenzoylamino)-L-alanine (308.5 mg, 65%) as a white solid.

Workup

  1. customthe solvent was evaporated
  2. additionTetrahydrofuran and water (75 mL each) were added
  3. temperatureThe cloudy white solution was heated at approx. 50° C. for 10 min
  4. waitto stand overnight at room temperature
  5. customThe solvents were evaporated
  6. dissolutionthe residue was dissolved in methanol/water (1:4; 60 mL)
  7. custompurified by HPLC in 10 mL portions

Sources & evidence

ORD record
ord-cc6c18c152734066a59091e0dd89d539
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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