Reaction #76834

Reaction equation

(R)-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)guanine

N,N-diethylaniline

phosphorous oxychloride

→

(R)-2-Amino-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)-6-chloropurine

Solvents

acetonitrile

Conditions

Workup

1. 1
   Temperatureunder reflux
2. 2
   OtherAfter 3 hours the reaction mixture was evaporated in vacuo
3. 3
   workup.DISSOLUTIONthe residue was dissolved in dichloromethane
4. 4
   workup.ADDITIONpoured into cold sodium hydrogen carbonate aqueous solution
5. 5
   OtherThe organic phase was evaporated
6. 6
   Otherpurified by silica gel column chromatography

Procedure

To a solution of (R)-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)guanine from step 2 of Example 1 (646 mg, 0.9 mmole) in acetonitrile were added tetramethylammonium chloride (427 mg, 2.7 mmole), N,N-diethylaniline (0.716 ml, 4.5 mmole) and phosphorous oxychloride (0.417 ml, 4.5 mmole). The reaction was kept under reflux and the progression monitored by TLC. After 3 hours the reaction mixture was evaporated in vacuo and the residue was dissolved in dichloromethane, then poured into cold sodium hydrogen carbonate aqueous solution. The organic phase was evaporated and purified by silica gel column chromatography. Yield: 251 mg.

Source