Sodium Hydroxide → 2-((2-tertbutoxycarbonylamino-3-(4-fluorophenyl)propionyl)-N-methylamino)-3-methylbutyric acid 2-(3-t-butyl-4-hydroxyphenyl)-1-(1,2,4-oxadiazol-5-yl)ethylamide

HRID 1988273Notes

Reaction equation

HRID 1988273 reaction equation
[NH:1]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C@H:2]([C:11]([N:13]([CH3:37])[C@H:14]([C:18]([NH:20][C@H:21]([C:34]([NH2:36])=[O:35])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[C:25]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:24]=1)=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][CH:5]=1.[CH3:45][N:46](C)C(=O)C.[OH-].[Na+].Cl.ON>O1CCOCC1.C(O)(=O)C.O.O>[C:30]([C:25]1[CH:24]=[C:23]([CH2:22][CH:21]([NH:20][C:18](=[O:19])[CH:14]([N:13]([C:11](=[O:12])[CH:2]([NH:1][C:38]([O:40][C:41]([CH3:42])([CH3:43])[CH3:44])=[O:39])[CH2:3][C:4]2[CH:5]=[CH:6][C:7]([F:10])=[CH:8][CH:9]=2)[CH3:37])[CH:15]([CH3:17])[CH3:16])[C:34]2[O:35][N:46]=[CH:45][N:36]=2)[CH:28]=[CH:27][C:26]=1[OH:29])([CH3:33])([CH3:31])[CH3:32]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 31374DimethylacetamideHCID 443297Hydroxyamine hydrochlorideHCID 131727517Boc-Phe(4-F)-N-Me-Val-Tyr(3-tBu)-NH2

Product 1

HCID 867609022-((2-tertbutoxycarbonylamino-3-(4-fluorophenyl)propionyl)-N-methylamino)-3-methylbutyric acid 2-(3-t-butyl-4-hydroxyphenyl)-1-(1,2,4-oxadiazol-5-yl)ethylamideYield 76%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 21899381Acetic acid--water (1/1)Solvent

Procedure

A solution of Boc-Phe(4-F)-N-Me-Val-Tyr(3-tBu)-NH2 (600 mg, 0.976 mmol) and N,N-dimethylacetamide (0.2 ml, 1.5 mmol) in dioxane (3 ml) was stirred at room temperature for 1 hour and mixed with a solution of sodium hydroxide (108 mg) and hydroxyamine hydrochloride (190 mg) in acetic acid/water (7 ml/3 ml). The mixture was stirred at room temperature for 10 min., mixed with water and filtered; a solution of the thus obtained precipitate in acetic acid/dioxane (10 ml/10 ml) was stirred at 60° C. overnight. The reaction mixture was mixed with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated to remove the solvent under reduced pressure; the thus obtained residue was subjected to silica gel column chromatography (developing solvent: ethyl acetate:n-hexane=1:1), giving the titled compound (474 mg, 76%).

Workup

  1. filtrationfiltered
  2. stirringa solution of the thus obtained precipitate in acetic acid/dioxane (10 ml/10 ml) was stirred at 60° C. overnight
  3. additionThe reaction mixture was mixed with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated
  8. customto remove the solvent under reduced pressure

Sources & evidence

ORD record
ord-2902be423cab4031a273ffe85431ba25
Source dataset
uspto-grants-2009_06
Patent number
US07553969B1

Reaction notes

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