2-Fluorothiophenol → 2-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]purin-9-yl}(4S,5S,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol

To a solution of 2-fluorothiophenol (38 mL, 406 mmol) in 2N sodium hydroxide (100 mL) was added 2-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]purin-9-yl}(4S,5S,3R)-5-(chloromethyl)oxolane-3,4-diol (15.0 g, 40.6 mmol) in N,N-dimethylformamide (120 mL). The mixture was warmed to 100 C for 4 hours, following the progress of the reaction by TLC. The N,N-dimethylformamide was removed under reduced pressure, and the remaining mixture was diluted with water (200 mL), neutralized with acetic acid, extracted with ethyl acetate (3×125 mL), and the combined organic layers were dried over MgSO4. After removing the solvent under reduced pressure the residue was triturated with diethyl ether and filtered, to afford 16 grams of 2-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]purin-9-yl}(4S,5S,3R)-5-[(2-fluorophenylthio)methyl]oxolane-3,4-diol as a white powder (85% yield).

1. temperatureThe mixture was warmed to 100 C for 4 hours
2. customthe progress of the reaction by TLC
3. customThe N,N-dimethylformamide was removed under reduced pressure
4. additionthe remaining mixture was diluted with water (200 mL)
5. extractionextracted with ethyl acetate (3×125 mL)
6. dry with materialthe combined organic layers were dried over MgSO4
7. customAfter removing the solvent under reduced pressure the residue
8. customwas triturated with diethyl ether
9. filtrationfiltered

ORD-Eintrag

ord-a2e76e5625634c26b1d422c5be5c866c

Quelldatensatz

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07300923B2