Methanol → HCID 46844020, compound

To a 250 mL dry round-bottomed flask was charged (2R,3R,4R,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-(benzoyloxymethyl)-4-fluoro-4-methyltetrahydrofuran-3-yl benzoate (12, 7.50 g, 14.26 mmol). Anhydrous methanol (30 mL) was added and a white suspension was formed. At 50° C., a solution of sodium methoxide in methanol (25%, 19.7 mL, 64.17 mmol) was added via a dry syringe under a nitrogen atmosphere. A white cloudy reaction mixture was formed. After 3.5 h at 50° C., the reaction was complete with no starting material left as shown by TLC test. The mixture was cooled down to room temperature and neutralized by addition of glacial acetic acid (3 mL). A white solid was filtered out and washed with methanol (3×5 mL). The filtrate was mixed with 20 g of silica gel and concentrated to dryness. The mixture was loaded in line with a silica gel cartridge and separated via column chromatography using a gradient of methanol in dichloromethane 0 to 15% MeOH. The product eluted out at 12% methanol in dichloromethane. The product containing fractions were combined, concentrated under reduced pressure and dried under vacuum (0.2 mmHg, 50° C., 24 h) to a white powder solid (4.45 g, 98% yield), mp 199-202° C.

1. customa white suspension was formed
2. customA white cloudy reaction mixture
3. customwas formed
4. waitleft
5. filtrationA white solid was filtered out
6. washwashed with methanol (3×5 mL)
7. additionThe filtrate was mixed with 20 g of silica gel
8. concentrationconcentrated to dryness
9. customseparated via column chromatography
10. washThe product eluted out at 12% methanol in dichloromethane
11. additionThe product containing fractions
12. concentrationconcentrated under reduced pressure

ORD record

ord-eab7623fd2be413b8f6054b28f769e88

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759510B2