Reaction #985281

Reaction equation

N9-cyclohexylethyl-8-hydroxymethyladenine

PBr3

N9-cyclohexylethyl-8-methoxycarbonyladenine

lithium aluminum hydride

→

N9-cyclohexylethyl-8-bromomethyl-adenine

Solvents

methylene chloride

tetrahydrofuran

Conditions

Workup

1. 1
   ExtractionExtraction and chromatography
2. 2
   Othergive N9-cyclohexylethyl-8-hydroxymethyladernine as a white solid
3. 3
   ExtractionExtraction and chromatography

Procedure

A mixture of N9-cyclohexylethyl-8-bromoadenine (1 mmol), tetrakis (triphenylphosphine)palladium (0.05 mmol), and triethylamine (5 mmol) in DMF in a sealed tube was warmed at 110° C. under 50 psi of carbon monoxide. After 24 h the cooled reaction mixture was evaporated and purified through chromatography to give N9-cyclohexylethyl-8-methoxycarbonyladenine as a yellow solid. Step B. A solution of N9-cyclohexylethyl-8-methoxycarbonyladenine (1 mmol) in tetrahydrofuran was treated with lithium aluminum hydride (1 mmol) at 0° C. for 1 h. Extraction and chromatography give N9-cyclohexylethyl-8-hydroxymethyladernine as a white solid. Step C. A solution of N9-cyclohexylethyl-8-hydroxymethyladenine (1 mmol) in methylene chloride was treated with PBr3 (1 mmol) at 25° C. for 1 h. Extraction and chromatography give N9-cyclohexylethyl-8-bromomethyl-adenine as a white solid. Step D. A solution of N9-cyclohexylethyl-8-bromomethyladenine (1 mmol) in DMF was treated with a solution of diethyl hydroxymethylphosphonate sodium salt (1 mmol) in DMF at 25° C. for 1 h. Extraction and chromatography gave N9-cyclohexylethyl-8-diethylphosphonomethoxy-methyladenine as a white solid. Step E. N9-cyclohexylethyl-8-diethylphosphonomethoxymethyladenine was subjected to Step F in Example 1.

Source