Trimethylsilyl triflate → (2R,3R,4R,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-5-((benzoyloxy)methyl)-3-methyltetrahydrofuran-3,4-diyl dibenzoate

HRID 530171Notes

Reaction equation

HRID 530171 reaction equation
C(O[C@H:10]1[C@@:14]([O:16][C:17](=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([CH3:15])[C@H:13]([O:25][C:26](=[O:33])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:12]([CH2:34][O:35][C:36](=[O:43])[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:11]1)(=O)C1C=CC=CC=1.[NH2:44][C:45]1[N:53]=[C:52]2[C:48]([NH:49][CH:50]=[N:51]2)=[C:47]([Cl:54])[N:46]=1.CCCCCCC=CCCC.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(=O)(O)[O-].[Na+]>C(#N)C>[C:17]([O:16][C@:14]1([CH3:15])[C@H:13]([O:25][C:26](=[O:33])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:12]([CH2:34][O:35][C:36](=[O:43])[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[O:11][C@H:10]1[N:51]1[CH:50]=[N:49][C:48]2[C:52]1=[N:53][C:45]([NH2:44])=[N:46][C:47]=2[Cl:54])(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 5

HCID 65367Trimethylsilyl triflateHCID 136496Undec-4-eneHCID 516892Sodium BicarbonateHCID 53603492-Amino-6-chloropurineHCID 108755601,2,3,5-Tetra-O-benzoyl-2-C-methyl-beta-D-ribofuranose

Product 1

HCID 58730438(2R,3R,4R,5R)-2-(2-amino-6-chloro-9H-purin-9-yl)-5-((benzoyloxy)methyl)-3-methyltetrahydrofuran-3,4-diyl dibenzoateYield 79%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

To a pre-cooled (0° C.) solution of (2S,3R,4R,5R)-5-(benzoyloxymethyl)-3-methyltetrahydrofuran-2,3,4-triyl tribenzoate (or 2,3,4,5-tetra-O-benzoyl-2-C-methyl-β-D-ribofuranose) (CarboSynth Ltd, 10.0 g, 17.22 mmol), 2-amino-6-chloropurine (Aldrich, 3.2 g, 18.87 mmol), and 1,8-diazabicycl[5.4.0]undec-7-ene (DBU) (7.7 mL, 51 mmol) in anhydrous acetonitrile (200 mL), was added trimethysilyl triflate (12.5 mL, 68.8 mmol) dropwise. The reaction mixture was then heated at 65° C. for 4 to 6 h, allowed to cool down to room temperature, poured into saturated aqueous sodium bicarbonate (300 mL), and extracted with dichloromethane (3×150 mL). The combined organic phase was dried over sodium sulfate and evaporated under reduced pressure. The residue was precipitated from dichloromethane and methanol, filtrated, the solid was washed 2 times with methanol and dried to give the desired compound (8.5 g, 79%) as a white solid (yields are from 65% (column) up to 90% (precipitation)).

Workup

  1. temperatureto cool down to room temperature
  2. extractionextracted with dichloromethane (3×150 mL)
  3. dry with materialThe combined organic phase was dried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was precipitated from dichloromethane and methanol
  6. filtrationfiltrated
  7. washthe solid was washed 2 times with methanol
  8. customdried

Sources & evidence

ORD record
ord-b0807a5cff974430adfaedd3ed01c923
Source dataset
uspto-grants-2016_05
Patent number
US09351989B2

Reaction notes

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