Tetraethyltin → Ammonium Hydroxide

HRID 471363Notes

Reaction equation

HRID 471363 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](CC)(CC)CC)[CH3:31]>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].[CH2:30]([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])[CH3:31]

Participants

7

Reactant 3

HCID 11704TetraethyltinHCID 13838HexamethyldisilazaneHCID 965448-Bromoadenosine

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 30069608-Ethyladenosine

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 tetraethyltin (0.59 mL, 3.0 mmol) and Pd(PPh3)4 (0.175 g, 0.15 mmol) were added. The reaction was allowed to stir at 130° C. for 16 h before cooling to room temperature. The reaction mixture 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-ethyl adenosine.

Workup

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

Sources & evidence

ORD record
ord-4ac6dee669c24bf486c0a8672befbe0b
Source dataset
uspto-grants-2014_01
Patent number
US08633168B2

Reaction notes

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