HCID 131720792, compound → HCID 131720795, compound

HRID 276145Notes

Reaction equation

HRID 276145 reaction equation
[NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].[CH2:7]([OH:14])[C:8]([NH2:13])([CH2:11][OH:12])[CH2:9][OH:10]>CN(C=O)C>[OH:6][C:4]([CH:2]([C:2]1[CH:4]=[CH:11][C:8]([CH2:9][CH:8]([CH3:9])[CH3:7])=[CH:7][CH:3]=1)[CH3:3])=[O:5].[NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].[CH2:7]([OH:14])[C:8]([NH2:13])([CH2:11][OH:12])[CH2:9][OH:10]

Participants

3

Reactant 1

HCID 131720792HCID 131720792, compound

Product 1

HCID 131720795HCID 131720795, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ibuprofen (3 g, 14.5 mmole) in DCM (50 ml), HOSu (2.49 g, 21.6 mmole) and DIEA (1.25 ml, 7.25 mmole) were added and the solution cooled to 0° C. DCC (3 g, 14.5 mmole) dissolved in DCM (20 ml) was dropped into the reaction mixture. It was stirred at 0° C. for 2 h followed by continued stirring at room temperature for 12 h to obtain the activated ester (ibuprofen-OSu) in 95% yield by HPLC. The DCU precipitate was filtered off and Ala-Tris (2.77 g, 14.5 mmole) dissolved in DMF (10 ml) was added to the reaction mixture and stirring continued at room temperature for 4 h. The title compound was formed in 70% yield by HPLC. RtA: 5.43. The solvents were removed under reduced pressure and the oily residue dissolved in DCM and washed with citric acid (4%), sodium bicarbonate (5%) and water. The DCM was dried (MgSO4) and evaporated to dryness, to obtain 5.4 g of an oily compound. The oily residue was a 50/50 racemized mixture which was identified by its 1HNMR spectrum. The doublet peak of methyl proton of alanine and ibuprofen of the diasteroisomers shifted away about 6 Hz from each other.

Workup

  1. filtrationThe DCU precipitate was filtered off
  2. additionwas added to the reaction mixture

Sources & evidence

ORD record
ord-5677e019e9a84e3c9bc1732d94679623
Source dataset
uspto-grants-2002_03
Patent number
US06353124B1

Reaction notes

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