Trimethylsilyl triflate → HCID 18336820, compound

HRID 2297676Notes

Reaction equation

HRID 2297676 reaction equation
[C:1]([O:4][C@H:5]1[C@@H:9]([O:10][C:11](=[O:13])[CH3:12])[CH:8](OC(=O)C)[O:7][C@@H:6]1[C:18]1[CH:22]=[C:21]([CH2:23][CH3:24])[O:20][N:19]=1)(=[O:3])[CH3:2].[Cl:25][C:26]1[N:34]=[C:33]2[C:29]([NH:30][CH:31]=[N:32]2)=[C:28]([Cl:35])[N:27]=1.N12CCCN=C1CCCCC2.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>C(#N)C>[C:11]([O:10][C@@H:9]1[C@H:5]([O:4][C:1](=[O:3])[CH3:2])[C@@H:6]([C:18]2[CH:22]=[C:21]([CH2:23][CH3:24])[O:20][N:19]=2)[O:7][C@H:8]1[N:32]1[CH:31]=[N:30][C:29]2[C:33]1=[N:34][C:26]([Cl:25])=[N:27][C:28]=2[Cl:35])(=[O:13])[CH3:12]

Participants

6

Reactant 4

HCID 65367Trimethylsilyl triflate2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 53244122,6-DichloropurineHCID 69827825HCID 69827825, compound

Product 1

HCID 18336820HCID 18336820, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

(2R,3R,4R)-4,5-bis(acetyloxy)-2-(5-ethylisoxazol-3-yl)tetrahydrofuran-3-yl acetate isomer 1 (193 mg) was dissolved in acetonitrile (5 ml) and treated sequentially with 2,6-dichloropurine (213 mg), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (0.186 ml) and trimethylsilyl trifluoromethanesulphonate (TMSOTf) (0.225 ml) via a syringe over 5 min. The clear yellow solution was stirred at 22° C. for 40 h, at 60° C. for 21 h, and at 80° C. for 6 h. The mixture was cooled to room temperature and more DBU (0.186 ml) and TMSOTf (0.225 ml) were added. After stirring at 22° C. for 36 h the yellow mixture was heated at 60° C. overnight and at 80° C. for 6 h. The solvents were removed in vacuo and the resultant brown oily solid taken up in ethyl acetate and washed with water (20 ml, 3:1). The aqueous layer was extracted with ethyl acetate and the combined organic layers dried (MgSO4) and evaporated in vacuo to afford a brown oily solid. The residue was triturated with dichloromethane and a white solid removed by filtration. Evaporation of the filtrate afforded a tan solid. Purification by flash chromatography on silica gel eluting with ether:cyclohexane (1:1) afforded the title compound as a white solid (161 mg).

Workup

  1. waitat 80° C. for 6 h
  2. temperatureThe mixture was cooled to room temperature
  3. stirringAfter stirring at 22° C. for 36 h the yellow mixture
  4. temperaturewas heated at 60° C. overnight and at 80° C. for 6 h
  5. customThe solvents were removed in vacuo
  6. washwashed with water (20 ml, 3:1)
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. dry with materialthe combined organic layers dried (MgSO4)
  9. customevaporated in vacuo
  10. customto afford a brown oily solid
  11. customThe residue was triturated with dichloromethane
  12. customa white solid removed by filtration
  13. customEvaporation of the filtrate
  14. customafforded a tan solid
  15. customPurification by flash chromatography on silica gel eluting with ether:cyclohexane (1:1)

Sources & evidence

ORD record
ord-5926d77302cf46e0b3e3abe78ab0cf1f
Source dataset
uspto-grants-2002_12
Patent number
US06492348B1

Reaction notes

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