N-(4-Bromobutyl)phthalimide → ethyl N-[(4-phthalimidobutyl)oxy]acetimidate
Reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[C:9]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]2[C:7]1=[O:16].[OH:17][N:18]=[C:19]([O:21][CH2:22][CH3:23])[CH3:20]>O1CCCC1>[C:10]1(=[O:11])[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][O:17][N:18]=[C:19]([O:21][CH2:22][CH3:23])[CH3:20])[C:7](=[O:16])[C:8]2=[CH:15][CH:14]=[CH:13][CH:12]=[C:9]12Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Briefly, N-(4-bromobutyl)phthalimide was treated with the anion of ethyl N-hydroxyacetimidate in tetrahydrofuran to yield ethyl N-[(4-phthalimidobutyl)oxy]acetimidate. The product was then treated with hydrazine to release the desired amine, ethyl N-[(4-aminobutyl)oxy]acetamidate, from the phthalimide. The desired amine was isolated from the crude product by removal of phthalazine-1,4-dione by filtration, and was coupled to biotin using dicyclohexyl carbodiimide and N-hydroxy succinimide in dimethylformamide. Acidic hydrolysis of the coupled product, ethyl N-[(4-biotinamidobutyl)oxy]acetamidate, gave the final product, N-(4-aminooxybutyl)biotinamide, V. Other analogous aminooxy linkers may be prepared by variations of the above synthetic procedure. The synthesis of biotin aminooxy linker V is described in more detail and summarized in the reaction scheme presented in Example 1.
Sources & evidence
- ORD record
- ord-d8c98f13d2524b5c922d20cbba1b0102
- Source dataset
- uspto-grants-1999_03
- Patent number
- US05880270
Reaction notes
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