Reacción #462905

Ecuación de reacción

methyl (4R, 7S)-7-amino-12,14-bis(tert-butyldimethylsilyloxy)-1,3,4,5,6,7,8,10-octahydro-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4-carboxylate

N-(tert-butoxycarbonyl)-L-serine

N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride

→

methyl (4R, 7S)-7-[(S)-2-(1-tert-butoxyformamido)-3-hydroxypropionylamino]-1,3,4,5,6,7,8,10-octahydro-12,14-dihydroxy-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4-carboxylate

Rendimiento 38.7%

Disolventes

acetonitrile

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   Lavadowashed successively with 0.5N hydrochloric acid, water, 5% sodium bicarbonate solution
2. 2
   SecadoThe organic layer was dried over sodium sulfate
3. 3
   Otroevaporated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in 2 ml of methanol
5. 5
   workup.ADDITION20 mg of ammonium fluoride were added
6. 6
   workup.STIRRINGthe mixture was stirred for 30 minutes at room temperature
7. 7
   workup.ADDITIONThe mixture was diluted with 40 ml of ethyl acetate
8. 8
   Lavadowashed with 30 ml of water
9. 9
   SecadoThe organic layer was dried over sodium sulfate
10. 10
    Otrothe solvent was evaporated in vacuo
11. 11
    OtroThe solid residue was triturated with 2 ml of ether
12. 12
    workup.ADDITIONhexane was added
13. 13
    Otrothe white solid was isolated by filtration

Procedimiento

To a solution of 61 mg of methyl (4R, 7S)-7-amino-12,14-bis(tert-butyldimethylsilyloxy)-1,3,4,5,6,7,8,10-octahydro-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4-carboxylate and 21 mg N-(tert-butoxycarbonyl)-L-serine in 2 ml of acetonitrile, cooled to 0° C., were added 20 mg of N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride. The mixture was stirred at 0° C. for 4 hours, then diluted with 30 ml of ethyl acetate, and washed successively with 0.5N hydrochloric acid, water, 5% sodium bicarbonate solution, and with brine. The organic layer was dried over sodium sulfate and evaporated in vacuo. The residue was dissolved in 2 ml of methanol, 20 mg of ammonium fluoride were added, and the mixture was stirred for 30 minutes at room temperature. The mixture was diluted with 40 ml of ethyl acetate and washed with 30 ml of water. The organic layer was dried over sodium sulfate, and the solvent was evaporated in vacuo. The solid residue was triturated with 2 ml of ether, then hexane was added, and the white solid was isolated by filtration to give 22 mg of methyl (4R, 7S)-7-[(S)-2-(1-tert-butoxyformamido)-3-hydroxypropionylamino]-1,3,4,5,6,7,8,10-octahydro-12,14-dihydroxy-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4-carboxylate.

Fuente