Reacción #53990

ord-f111c92c1d8f42b1bfcc3068d7013a61

Ecuación de reacción

COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CC(C)C)NC(=O)OCc4ccccc4)C(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]3O[Si](C)(C)C(C)(C)C)c2=O)cc1
tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate
O=[N+]([O-])[O-].O=[N+]([O-])[O-].O=[N+]([O-])[O-].O=[N+]([O-])[O-].O=[N+]([O-])[O-].[Ce+4].[NH4+]
ammonium cerium(IV) nitrate
[Cl-].[Na+]
sodium chloride
→
CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)NCCCN[C@H](C(=O)OC(C)(C)C)[C@@H](O)C1O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](O[Si](C)(C)C(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2,4-dioxo -3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate
Rendimiento 25.0%

Reactantes

COc1ccc(Cn2c(=O)ccn([C@@H]3OC([C@H](O)[C@H](NCCCNC(=O)[C@H](CC(C)C)NC(=O)OCc4ccccc4)C(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]3O[Si](C)(C)C(C)(C)C)c2=O)cc1
tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate
O=[N+]([O-])[O-].O=[N+]([O-])[O-].O=[N+]([O-])[O-].O=[N+]([O-])[O-].O=[N+]([O-])[O-].[Ce+4].[NH4+]
ammonium cerium(IV) nitrate
[Cl-].[Na+]
sodium chloride

Reactivos

Ninguno

Disolventes

CC#N
acetonitrile
O
water

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    ExtracciónThe aqueous layer was extracted with ethyl acetate (3×75 mL)
  2. 2
    LavadoThe combined extracts were washed with saturated sodium chloride
  3. 3
    Secadodried over sodium sulfate
  4. 4
    Filtraciónfiltered
  5. 5
    Concentraciónconcentrated in vacuo
  6. 6
    OtroThe resultant residue was chromatographed (flash column, silica gel, 5% methanol in methylene chloride)

Procedimiento

To a solution of tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (420 mg, 0.409 mmol, obtained from Example 4) in acetonitrile (20 ml) was added a solution of ammonium cerium(IV) nitrate (898 mg, 1.6 mmol) in water (4 ml). The resulting solution was stirred for 48 hours at room temperature, and saturated sodium chloride aqueous solution was added. The aqueous layer was extracted with ethyl acetate (3×75 mL). The combined extracts were washed with saturated sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuo. The resultant residue was chromatographed (flash column, silica gel, 5% methanol in methylene chloride) to provide tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2,4-dioxo -3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (91 mg, 25%) as a pale tan amorphous solid.

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US06858591B2uspto-grants-2005_02