Hexamethyldisilazane → Ammonium Hydroxide

Participants

Reaction Steps

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.

Provenance & Evidence