Lithium hydroxide, monohydrate → 3-[3-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)ureido]benzoic acid

HRID 1979442Notes

Reaction equation

HRID 1979442 reaction equation
[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[N:12]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH2:11][CH:10]([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([O:38]CC)=[O:37])[CH:31]=2)=[O:28])[C:9]1=[O:41])=[O:6])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>CO>[C:1]([C:5]([CH2:7][N:8]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[N:12]([CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)[CH2:11][CH:10]([NH:26][C:27](=[O:28])[NH:29][C:30]2[CH:31]=[C:32]([CH:33]=[CH:34][CH:35]=2)[C:36]([OH:38])=[O:37])[C:9]1=[O:41])=[O:6])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 212018501-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-ethoxycarbonylphenyl)urea

Product 1

HCID 212015683-[3-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)ureido]benzoic acidYield 85.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

1-(1-tert-Butylcarbonylmethyl-2-oxo-5-cyclohexyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)-3-(3-ethoxycarbonylphenyl)urea (370 mg) was suspended in methanol (5 ml), aqueous lithium hydroxide monohydrate (142 mg) solution (5 ml) was added to the suspension, and the mixture was stirred at 50° C. for 2 hours. The reaction mixture was filtrated. The filtrate was acidified with 1N hydrochloric acid, and methanol was evaporated. The mixture was extracted with ethyl acetate, the organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure. The residue was recrystallized from isopropyl alcohol, to thereby obtain 300 mg of the title compound (Yield: 83%).

Workup

  1. filtrationThe reaction mixture was filtrated
  2. customwas evaporated
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was recrystallized from isopropyl alcohol

Sources & evidence

ORD record
ord-1f32bc56de4e438e82cdc9c2b93c2c01
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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