Methyl morpholine oxide → 2'-O-(2-Hydroxyethyl)-3',5'-bis(tert-butyldiphenylsilyl)guanosine

HRID 365946Notes

Reaction equation

HRID 365946 reaction equation
[CH2:1]([O:4][C@@H:5]1[C@:9]([Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([OH:10])[C@@H:8]([CH:28]([Si:30]([C:43]([CH3:46])([CH3:45])[CH3:44])([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[OH:29])[O:7][C@H:6]1[N:47]1[C:57]2[N:56]=[C:54]([NH2:55])[NH:53][C:51](=[O:52])[C:50]=2[N:49]=[CH:48]1)[CH:2]=C.C[N+]1([O-])CC[O:62]CC1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.[Os](=O)(=O)(=O)=O.CC(C)=O>[OH:62][CH2:2][CH2:1][O:4][C@@H:5]1[C@:9]([Si:11]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)([OH:10])[C@@H:8]([CH:28]([Si:30]([C:43]([CH3:46])([CH3:44])[CH3:45])([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[OH:29])[O:7][C@H:6]1[N:47]1[C:57]2[N:56]=[C:54]([NH2:55])[NH:53][C:51](=[O:52])[C:50]=2[N:49]=[CH:48]1

Participants

8

Reactant 4

HCID 82029Methyl morpholine oxideHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 136347713HCID 136347713, compound

Product 1

HCID 1361616182'-O-(2-Hydroxyethyl)-3',5'-bis(tert-butyldiphenylsilyl)guanosineYield 72%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

Compound 124 (9 g, 11.23 mmol) was dissolved in CH2Cl2 (80 mL). To the clear solution acetone (50 mL), 4-methyl morpholine-N-oxide (1.89 g, 16.17 mmol) was added. The reaction flask was protected from light. Thus 4% aqueous solution of osmium tetroxide was added and the reaction mixture was stirred at room temperature for 6 hr. Reaction volume was concentrated to half and ethyl acetate (50 mL) was added. It was then washed with water (30 mL) and brine (30 mL). Ethyl acetate layer was dried over anhydrous Na2SO4 and evaporated to dryness. Residue was then dissolved in CH2Cl2 and Na2O4 adsorbed on silica (21.17 g, 2 g/mmol) was added and stirred with the reaction mixture for 30 min. The reaction mixture was filtered and silica was washed thoroughly with CH2Cl2. Combined CH2Cl2 layer was evaporated to dryness. Residue was then dissolved in dissolved in 1M pyridinium-p-toluene sulfonate (PPTS) in dry MeOH (99.5 mL) under inert atmosphere. To the clear solution sodium cyanoborohydride (1.14 g, 18.2 mmol) was added and stirred at room temperature for 4 hr. 5% aqueous sodium bicarbonate (50 mL) was added to the reaction mixture slowly and extracted with ethyl acetate (2×50 mL). Ethyl acetate layer was dried over anhydrous Na2SO4 and evaporated to dryness. Residue placed on a flash column and eluted with 10% MeOH in CH2Cl2 to yield 125 (6.46 g, 72% yield) MS (Electrospray-) m/e 802 (M-H⊕)

Workup

  1. customReaction volume
  2. concentrationwas concentrated to half and ethyl acetate (50 mL)
  3. additionwas added
  4. washIt was then washed with water (30 mL) and brine (30 mL)
  5. dry with materialEthyl acetate layer was dried over anhydrous Na2SO4
  6. customevaporated to dryness
  7. dissolutionResidue was then dissolved in CH2Cl2
  8. additionwas added
  9. stirringstirred with the reaction mixture for 30 min
  10. filtrationThe reaction mixture was filtered
  11. washsilica was washed thoroughly with CH2Cl2
  12. customCombined CH2Cl2 layer was evaporated to dryness
  13. dissolutionResidue was then dissolved
  14. dissolutionin dissolved in 1M pyridinium-p-toluene sulfonate (PPTS) in dry MeOH (99.5 mL) under inert atmosphere
  15. stirringstirred at room temperature for 4 hr
  16. extractionextracted with ethyl acetate (2×50 mL)
  17. dry with materialEthyl acetate layer was dried over anhydrous Na2SO4
  18. customevaporated to dryness
  19. washeluted with 10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-c562ae5574cb4b3e91a7d9f99ef9445d
Source dataset
uspto-grants-2000_10
Patent number
US06127533

Reaction notes

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