Tetrahydrofuran → HCID 178456805, compound

Argon was bubbled through a mixture of (S)-tert-butyl (1-(6-bromo-1-(methoxymethyl)-1H-benzo[d]imidazol-2-yl)propyl)carbamate (Preparation 19, 218 mg, 0.55 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(11) (45.0 mg, 0.0615 mmol), and cyclobutylzinc bromide in tetrahydrofuran (0.5 M, 5.5 mL, 2.8 mmol) for 5 minutes. The mixture was then heated at reflux for 18 hours. After cooling, the reaction was concentrated in vacuo, redissolved in ethyl acetate, and washed with water and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient to afford the fully protected intermediate as a brown oil. To this oil, cooled in an ice water bath, was added boron tribromide (0.5 mL, 5 mmol) and the reaction was allowed to warm to room temperature and stirred for 5 days. The resulting mixture was then purified by preparative HPLC to provide the title compound (32 mg, 13%) as a white solid.

1. temperatureThe mixture was then heated
2. temperatureat reflux for 18 hours
3. temperatureAfter cooling
4. concentrationthe reaction was concentrated in vacuo
5. dissolutionredissolved in ethyl acetate
6. washwashed with water and brine
7. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified
11. washeluting with a 0-100% ethyl acetate/hexanes gradient
12. customto afford the fully protected intermediate as a brown oil
13. temperatureTo this oil, cooled in an ice water bath
14. customThe resulting mixture was then purified by preparative HPLC

ORD record

ord-8146dbf92bc54f26850592802804c533

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927587B2