Sodium Hydroxide → (2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide

HRID 1489792Notes

Reaction equation

HRID 1489792 reaction equation
[C:1]1([NH:7][C:8](=[O:45])[C@H:9]([CH2:41][CH:42]([CH3:44])[CH3:43])[NH:10][C:11](=[O:40])[CH:12]([CH2:21][P:22]([CH2:26][CH2:27][CH2:28][CH2:29][N:30]2[CH2:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]2=[O:39])([O:24]C)=[O:23])[CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>CO.Cl>[C:1]1([NH:7][C:8](=[O:45])[C@H:9]([CH2:41][CH:42]([CH3:43])[CH3:44])[NH:10][C:11](=[O:40])[CH:12]([CH2:21][P:22]([CH2:26][CH2:27][CH2:28][CH2:29][N:30]2[CH2:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]2=[O:39])([OH:24])=[O:23])[CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 57286101HCID 57286101, compound

Product 1

HCID 57084392(2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)hydroxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamideYield 88%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

(2-(((4-(1,3-Dihydro-1-oxo-2H-isoindol-2-yl)butyl)methoxyphosphinyl)methyl)-4-phenylbutanoyl)-L-leucine N-phenylamide (0.31 g, 0.49 mmol) from Step C was dissolved in methanol (10 mL). The solution was cooled in an ice bath and 2N aqueous sodium hydroxide (5 mL, 10 mmol) was added. The solution was allowed to warm to room temperature and was stirred for an additional 12 h before being diluted with 2N aqueous hydrochloric acid (40 mL) and extracted with ethyl acetate (75 mL). The organic extract was washed with saturated aqueous sodium chloride (25 mL), dried (sodium sulfate), and evaporated. The crude product was purified by high pressure liquid chromatography on a.22 mm×25 cm reverse phase column (Whatman ODS-3, Partisil 10) eluting with 45% acetonitrile/55% water/0.05% trifluoroacetic acid (flow rate of 20 mL/min, detection at 250 nm). Evaporation of appropriate fractions gave 264 mg the desired product (88% yield) as a colorless brittle foam.

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. extractionextracted with ethyl acetate (75 mL)
  3. extractionThe organic extract
  4. washwas washed with saturated aqueous sodium chloride (25 mL)
  5. dry with materialdried (sodium sulfate)
  6. customevaporated
  7. customThe crude product was purified by high pressure liquid chromatography on a
  8. wash22 mm×25 cm reverse phase column (Whatman ODS-3, Partisil 10) eluting with 45% acetonitrile/55% water/0.05% trifluoroacetic acid (flow rate of 20 mL/min, detection at 250 nm)
  9. customEvaporation of appropriate fractions

Sources & evidence

ORD record
ord-f84e7dd3954249e09a33a82f8f7a1f88
Source dataset
uspto-grants-1997_10
Patent number
US05679700

Reaction notes

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