p-Chlorophenethylic alcohol → Sonedenoson

Temperature

50 °C

To a 250-mL, three-neck round bottom flask was added 2-chloro-2′,3′,5′-tri-O-(triethylsilyl)adenosine (5.0 g, 7.8 mmol, Example 4) and 2-(4-chlorophenyl)ethanol (15 mL). The mixture was flushed with nitrogen for 5–10 minutes, then heated to 50° C. To this mixture was added sodium hydride (1.56 g, 39 mmol, as a 60% dispersion in mineral oil) at such a rate as to avoid excessive gas evolution. The reaction was maintained at 50° C. for 20 hours, at which time HPLC indicated complete conversion to the fully deprotected, alkylated product. The reaction was then cooled to room temperature, carefully quenched with water (40 mL), and extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with brine (120 mL), dried (MgSO4), filtered, and concentrated under reduced pressure to afford a clear oil. This material was purified by passing through a plug of silica gel, eluting with CH2Cl2, 3% methanol in CH2Cl2, and 10% methanol in CH2Cl2. Those fractions containing products were combined and evaporated to dryness, affording the desired product as a white solid. 680 mg (21%).m.p.: 114–120° C.

1. customThe mixture was flushed with nitrogen for 5–10 minutes
2. additionTo this mixture was added sodium hydride (1.56 g, 39 mmol
3. temperatureThe reaction was maintained at 50° C. for 20 hours, at which time HPLC
4. temperatureThe reaction was then cooled to room temperature
5. customcarefully quenched with water (40 mL)
6. extractionextracted with ethyl acetate (3×100 mL)
7. washThe combined organic extracts were washed with brine (120 mL)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto afford a clear oil
12. customThis material was purified
13. washeluting with CH2Cl2, 3% methanol in CH2Cl2, and 10% methanol in CH2Cl2
14. additionThose fractions containing products
15. customevaporated to dryness

ORD record

ord-b9acbd90263043e3bece94fd99989c97

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07342003B2