Uracil → 2',3',5'-tri-O-benzoyl-2'-C-methyluridine

HRID 595455Notes

Reaction equation

HRID 595455 reaction equation
[NH:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].C(O[C@@H:18]1[O:40][C@H:39]([CH2:41][O:42][C:43](=[O:50])[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C@@H:29]([O:30][C:31](=[O:38])[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@@:19]1([CH3:51])[O:20][C:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=O)C1C=CC=CC=1.C([O-])(O)=O.[Na+]>C(#N)C.CCOC(C)=O>[C:21]([O:20][C@:19]1([CH3:51])[C@H:29]([O:30][C:31](=[O:38])[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@@H:39]([CH2:41][O:42][C:43](=[O:50])[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[O:40][C@H:18]1[N:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3])(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 1174UracilHCID 516892Sodium BicarbonateHCID 108755601,2,3,5-Tetra-O-benzoyl-2-C-methyl-beta-D-ribofuranose

Product 1

HCID 114217372',3',5'-tri-O-benzoyl-2'-C-methyluridineYield 80%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Compound 57 may be prepared according to Scheme 7, above. To a solution of uracil (4 g) in acetonitrile (120 ml) was added BSA (18 ml) and the mixture was stirred at 100° C. for 30 minutes. After cooling to room temperature, 1,2,3,5-tetra-O-benzoyl-2-C-methyl-β-D-ribofuranose (10 g) in acetonitrile (120 ml) and 5 nCl4 (7 ml) were added. The reaction mixture was stirred at 100° C. for 4 hours. The mixture was diluted with EtOAc and a saturated solution of NaHCO3 was added at 0° C. followed by filtration on celite. The filtrate was extracted with EtOAc and the organic layer was washed with a saturated solution of NaHCO3. After drying over Na2SO4 and filtration, the organic layer was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0→20% EtOAc in dichloromethane to yield 2′,3′,5′-tri-O-benzoyl-2′-C-methyluridine (80%). 2′,3′,5′-tri-O-benzoyl-2′-C-methyluridine was characterized by the following spectroscopic data: MS (ESI, EI+) m/z=571.2 (MH+).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringThe reaction mixture was stirred at 100° C. for 4 hours
  3. filtrationfollowed by filtration on celite
  4. extractionThe filtrate was extracted with EtOAc
  5. washthe organic layer was washed with a saturated solution of NaHCO3
  6. dry with materialAfter drying over Na2SO4 and filtration
  7. concentrationthe organic layer was concentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with 0→20% EtOAc in dichloromethane

Sources & evidence

ORD record
ord-bf77954dbed94524a8e9b69dc2b1b662
Source dataset
uspto-grants-2016_01
Patent number
US09243025B2

Reaction notes

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