Lithium Hydroxide → 3-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine

HRID 2270834Notes

Reaction equation

HRID 2270834 reaction equation
[C:1]([NH:9][CH2:10][C@@H:11]([C:33]([O:35]C)=[O:34])[NH:12][C:13](=[O:32])[C:14]1[CH:19]=[CH:18][C:17]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:21])=[CH:16][C:15]=1[Cl:31])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+]>O1CCCC1.CO.O>[C:1]([NH:9][CH2:10][C@@H:11]([C:33]([OH:35])=[O:34])[NH:12][C:13](=[O:32])[C:14]1[CH:19]=[CH:18][C:17]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[O:21])=[CH:16][C:15]=1[Cl:31])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 1317230313-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl) methyl]amino]carbonyl]benzoyl]-L-alanine, methyl ester

Product 1

HCID 100287563-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanineYield 68.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of 3-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine, methyl ester (10.7 g, 21.0 mmol) in tetrahydrofuran/methanol (3:1; 80 mL) was added to a stirred solution of lithium hydroxide monhydrate (2.65 g, 63.0 mmol) in water (40 mL) at room temperature. The reaction was stirred at room temperature overnight and then concentrated to remove methanol and tetrahydrofuran. Water (150 mL) was added and the mixture was cooled to between 0 and −5° C. The mixture was acidified to pH 3 with concentrated HCl and stirred for 10 min. The mixture was extracted twice with ethyl acetate, and the combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated to give 3-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine (7.1 g). The drying agent was extracted with ethyl acetate/methanol (50:3; 2×106 mL) to give a further quantity of the product (3.3 g). Overall yield:10.4 g (quantitative).

Workup

  1. concentrationconcentrated
  2. customto remove methanol and tetrahydrofuran
  3. additionWater (150 mL) was added
  4. temperaturethe mixture was cooled to between 0 and −5° C
  5. stirringstirred for 10 min
  6. extractionThe mixture was extracted twice with ethyl acetate
  7. washthe combined organic layers were washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated

Sources & evidence

ORD record
ord-09de0d6d58f4437888e1f9095b7904a8
Source dataset
uspto-grants-2001_12
Patent number
US06331640B1

Reaction notes

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