Imidazole → HCID 20872903, compound

Temperature

0 °C

A solution of the imidazole from Preparation 76 (4.9 g, 44.6 mmol) in tetrahydrofuran (20 ml) was added dropwise to a solution of sodium hydride (1.96 g, 60% dispersion in mineral oil, 49.1 mmol) in tetrahydrofuran (20 ml) and, once addition was complete, the solution was stirred for an hour. The solution was cooled to 0° C. and 2-(trimethylsilyl)ethoxymethyl chloride (8.28 ml, 46.8 mmol) was added dropwise over 20 minutes. The reaction mixture was stirred at room temperature for 18 hours, then concentrated under reduced pressure. The residue was partitioned between ether and water, the layers separated, and the aqueous phase extracted with ether. The combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The residual brown oil was purified by column chromatography on silica gel, eluting with dichloromethane:methanol (95:5), to afford the title compounds of Preparation 71 and 72 respectively in a regioisomeric mixture of 3:1, 7 g, 65% yield.

1. stirringThe reaction mixture was stirred at room temperature for 18 hours
2. concentrationconcentrated under reduced pressure
3. customThe residue was partitioned between ether and water
4. customthe layers separated
5. extractionthe aqueous phase extracted with ether
6. washThe combined organic extracts were washed with brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residual brown oil was purified by column chromatography on silica gel
11. washeluting with dichloromethane:methanol (95:5)
12. customto afford
13. additionrespectively in a regioisomeric mixture of 3:1, 7 g, 65% yield

ORD record

ord-22cbbaba6d0f462894242d6f29089523

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949577B2