Sodium hydride → 6-bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole

In a round-bottomed flask 6-bromo-1H-indazole (0.70 g, 3.55 mmol) was dissolved in DMF (7.5 ml). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 172 mg, 4.3 mmol) was added). The reaction mixture was warmed to room temperature and stirred for 30 min then cooled back to 0° C. and SEM-Cl (0.76 ml, 4.28 mmol) was slowly added. After the addition was complete, the ice bath was removed and the reaction mixture was warmed to room temperature. After 1.5 h the reaction was quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/Hexanes (gradient 0-10% EtOAc) to give 802 mg (69%) of 6-bromo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole as a light yellow oil.

1. temperatureThe reaction mixture was warmed to room temperature
2. temperaturethen cooled back to 0° C.
3. additionAfter the addition
4. customthe ice bath was removed
5. temperaturethe reaction mixture was warmed to room temperature
6. customAfter 1.5 h the reaction was quenched with water
7. extractionextracted with diethyl ether (2×)
8. washThe combined organic layers were washed twice with water and once with brine
9. dry with materialthen dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was chromatographed over silica gel with EtOAc/Hexanes (gradient 0-10% EtOAc)

ORD record

ord-31e08321afa54c9e94d4e7503a8b71a5

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2