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

HRID 393063Notes

Reaction equation

HRID 393063 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-3b1ef471bc7e4ee5b998e8d45cff0d5d
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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