Lithium hydroxide, monohydrate → (R)-3-(3,4-diethyl-phenyl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid

HRID 644315Notes

Reaction equation

HRID 644315 reaction equation
[CH2:1]([C:3]1[CH:4]=[C:5]([CH2:11][C@@H:12]([NH:17][C:18]([N:20]2[CH2:25][CH2:24][CH:23]([N:26]3[CH2:32][CH2:31][C:30]4[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=4[NH:28][C:27]3=[O:37])[CH2:22][CH2:21]2)=[O:19])[C:13]([O:15]C)=[O:14])[CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10])[CH3:2].O.[OH-].[Li+]>C1COCC1.O>[CH2:1]([C:3]1[CH:4]=[C:5]([CH2:11][C@@H:12]([NH:17][C:18]([N:20]2[CH2:21][CH2:22][CH:23]([N:26]3[CH2:32][CH2:31][C:30]4[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=4[NH:28][C:27]3=[O:37])[CH2:24][CH2:25]2)=[O:19])[C:13]([OH:15])=[O:14])[CH:6]=[CH:7][C:8]=1[CH2:9][CH3:10])[CH3:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 69711722methyl (R)-3-(3,4-diethyl-phenyl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionate

Product 1

HCID 68579001(R)-3-(3,4-diethyl-phenyl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

74.4 g (0.147 mol) methyl (R)-3-(3,4-diethyl-phenyl)-2-{[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyl]-amino}-propionate dissolved in 600 mL THF was combined with 5.4 g (0.221 mol) lithium hydroxide hydrate in 300 mL water while cooling with an ice bath and stirred overnight at RT. The reaction mixture was evaporated down under reduced pressure, 300 mL water was added and the mixture was extracted three times with 200 mL EtOAc. The aqueous phase was freed from the organic solvent under reduced pressure and combined with 500 mL 2 M HCl with stirring and cooling with the ice bath. The precipitate formed was suction filtered, washed with water and dried.

Workup

  1. temperaturewhile cooling with an ice bath
  2. customThe reaction mixture was evaporated down under reduced pressure, 300 mL water
  3. additionwas added
  4. extractionthe mixture was extracted three times with 200 mL EtOAc
  5. stirringwith stirring
  6. temperaturecooling with the ice bath
  7. customThe precipitate formed
  8. filtrationfiltered
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-f2bbd87e4fe946c884f6c0966915ad61
Source dataset
uspto-grants-2010_04
Patent number
US07700589B2

Reaction notes

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