3-Aminobenzoic acid, monosodium salt → Z-360

HRID 352382Notes

Reaction equation

HRID 352382 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([O-:7])=[O:6].[Na+].[C:12]([C:16]([CH2:18][N:19]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]([CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:22][C@@H:21]([NH:36][C:37](OC2C=CC=CC=2)=[O:38])[C:20]1=[O:46])=[O:17])([CH3:15])([CH3:14])[CH3:13]>CN(C)C1C=CN=CC=1.CS(C)=O>[C:12]([C:16]([CH2:18][N:19]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[N:23]([CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:22][C@@H:21]([NH:36][C:37](=[O:38])[NH:1][C:2]2[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=2)[C:5]([OH:7])=[O:6])[C:20]1=[O:46])=[O:17])([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 2

HCID 236623443-Aminobenzoic acid, monosodium saltHCID 69908453(R)-(-)-1-tert-butylcarbonylmethyl-2-oxo-3-phenoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

Product 1

HCID 9872609Z-360Yield 70.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Under an argon atmosphere, 2.0 g of sodium 3-aminobenzoate, 77 mg of 4-dimethylaminopyridine and 3.0 g of Molecular Sieves 3A were added to a solution of 3.0 g of (R)-(−)-1-tert-butylcarbonylmethyl-2-oxo-3-phenoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine in 30 ml of anhydrous dimethylsulfoxide. The mixture was stirred at room temperature for 15 hours. After filtration of the reaction mixture, ice water and a 1N aqueous solution of sodium hydroxide were added to the filtrate. The mixture was extracted with ethyl acetate. The organic layer was washed successively with a 1N aqueous solution of sodium hydroxide, 1N hydrochloric acid and brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. To the residue was added a mixed solvent of ethanol and water (2:1). Crystals so precipitated were collected by filtration, whereby 2.32 g of the title compound was obtained.

Workup

  1. filtrationAfter filtration of the reaction mixture, ice water
  2. additiona 1N aqueous solution of sodium hydroxide were added to the filtrate
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed successively with a 1N aqueous solution of sodium hydroxide, 1N hydrochloric acid and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. additionTo the residue was added a mixed solvent of ethanol and water (2:1)
  8. customCrystals so precipitated
  9. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-b81c765511984f7a95f5d8544849710d
Source dataset
uspto-grants-2004_06
Patent number
US06747022B2

Reaction notes

Loading…