Hexamethyldisilazane → Ammonium Hydroxide

HRID 471364Notes

Reaction equation

HRID 471364 reaction equation
Br[C:2]1[N:3]([C:13]2[N:14]=[CH:15][N:16]=[C:17]([NH2:20])[C:18]=2[N:19]=1)[C@@H:4]1[O:12][C@H:9]([CH2:10][OH:11])[C@@H:7]([OH:8])[C@H:5]1[OH:6].C[Si](C)(C)N[Si](C)(C)C.[CH2:30]([Sn](CCCC)(CCCC)C=CC)[CH2:31][CH2:32]C>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH4+:3].[OH-:6].[CH:30]([C:2]1[N:3]([C:13]2[N:14]=[CH:15][N:16]=[C:17]([NH2:20])[C:18]=2[N:19]=1)[C@@H:4]1[O:12][C@H:9]([CH2:10][OH:11])[C@@H:7]([OH:8])[C@H:5]1[OH:6])=[CH:31][CH3:32]

Participants

7

Reactant 3

HCID 13838HexamethyldisilazaneHCID 965448-BromoadenosineHCID 57369809Stannane, tributyl-1-propenyl-

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 684997398-Propenyl adenosine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 8-Bromoadenosine (0.5 g, 1.5 mmol) and hexamethyldisilazane (5 mL) in 1,4-dioxane (10 mL) was heated overnight at 80° C. The reaction was cooled to room temperature, concentrated in vacuo, and azeotroped with toluene. The residue was taken up in NMP (3 mL) and tri-n-butylpropenyltin (1.0 g, 3.0 mmol) and Pd(PPh3)4 (0.175 g, 0.15 mmol) were added. The reaction was heated at 190° C. under microwave conditions for 0.5 h before cooling to room temperature. The catalyst was filtered through celite washing with EtOAc. The filtrate was partitioned between H2O and EtOAc. The aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was taken up in MeOH:H2O (4:1) (25 mL) and ammonium chloride was added (400 mg). The reaction was heated at 65° C. for 3 h. When judged complete by TLC, the reaction was concentrated in vacuo and was subjected to silica gel column chromatography running 0-25% MeOH:DCM with 0.1% NH4OH to afford 8-propenyl adenosine. The compound from the previous step was taken up in EtOH:H2O (3:1) (4 mL) and TFA (5 drops) and hydrogenated under H2 atmosphere in the presence of Pd/C 10% (20% w/w) at room temperature overnight. The catalyst was filtered off and the filtrate evaporated in vacuo. The 8-propyl adenosine was used without further purification.

Workup

  1. concentrationconcentrated in vacuo
  2. customazeotroped with toluene
  3. temperatureThe reaction was heated at 190° C. under microwave conditions for 0.5 h
  4. temperaturebefore cooling to room temperature
  5. filtrationThe catalyst was filtered
  6. washthrough celite washing with EtOAc
  7. customThe filtrate was partitioned between H2O and EtOAc
  8. extractionThe aqueous layer was extracted with EtOAc (2×20 mL)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. additionammonium chloride was added (400 mg)
  13. temperatureThe reaction was heated at 65° C. for 3 h
  14. concentrationthe reaction was concentrated in vacuo

Sources & evidence

ORD record
ord-4739334ce59a468588c94171597d7555
Source dataset
uspto-grants-2014_01
Patent number
US08633168B2

Reaction notes

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