Sodium hydride → HCID 131736629, compound

Temperature

0 °C

A flame-dried 25 mL round bottom flask was charged with NaH (0.092 g, 2.295 mmol) and then THF (4.17 mL) was added to give a gray suspension. The suspension was cooled to 0° C. and then a clear, yellow solution of 135B (0.9 g, 2.086 mmol) in THF (4.17 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 30 min and then allowed to warm to rt and stirring was continued at rt for additional 0.5 h. The yellow suspension was again cooled to 0° C. and then SEM-Cl (0.370 mL, 2.086 mmol) was added dropwise. The resulting cloudy reaction mixture was stirred at 0° C. After 1 h, the reaction was stopped and quenched with saturated NH4Cl followed by dilution with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4, filtered, and concentrated. The yellow oil weighing 1.6 g was purified by silica gel chromatography. The desired product from the reaction was obtained as yellow foam (0.424 g, 36%). MS (ESI) m/z: 562.0 (M+H)+. 1D NOE confirmed the regioisomeric position of SEM on the imidazole ring.

1. customto give a gray suspension
2. temperatureto warm to rt
3. stirringstirring
4. waitwas continued at rt for additional 0.5 h
5. temperatureThe yellow suspension was again cooled to 0° C.
6. customThe resulting cloudy reaction mixture
7. stirringwas stirred at 0° C
8. waitAfter 1 h
9. customquenched with saturated NH4Cl
10. customThe layers were separated
11. extractionthe aqueous layer was extracted with EtOAc
12. washThe combined organic layers were washed with saturated NaHCO3, brine
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated
16. customwas purified by silica gel chromatography

ORD record

ord-834cf3ccb2414ca99637a00c43315875

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409908B2