Ammonia → 5-Bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-ol

Temperature

35 °C

5-bromo-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole (0.54 g, 2.01 mmol) was dissolved in dichloromethane (12 mL) under N2. A 1M BBr3 solution in DCM (12 mL, 12 mmol) was added dropwise over 1 min. The resulting stirred suspension was heated to 35° C. After 5 h, the reaction mixture was cooled in an ice water bath. A 7M ammonia in MeOH solution (7.5 mL, 53 mmol) was then added over 2 min via syringe. The mixture was stirred 5 min and was removed from the ice bath. After an additional 10 min, the mixture was concentrated in vacuo, and the crude product was dissolved in MeOH (30 mL) and was concentrated in vacuo. The resulting crude solids were suspended in 20% MeOH in DCM (30 mL) and were filter through a short pad of silica, eluting with 20% MeOH in DCM. Filtrate was concentrated in vacuo, and the crude product was adsorbed onto silica gel. Purification by silica gel chromatography (0-20% MeOH in DCM) gave 5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-ol (2.73). LCMS-ES r (m/z): [m+H]+ calcd for C10H10BrN2O: 253.00; found: 253.14.

1. temperaturethe reaction mixture was cooled in an ice water bath
2. stirringThe mixture was stirred 5 min
3. customwas removed from the ice bath
4. waitAfter an additional 10 min
5. concentrationthe mixture was concentrated in vacuo
6. dissolutionthe crude product was dissolved in MeOH (30 mL)
7. concentrationwas concentrated in vacuo
8. filtrationwere filter through a short pad of silica
9. washeluting with 20% MeOH in DCM
10. concentrationFiltrate was concentrated in vacuo
11. customPurification by silica gel chromatography (0-20% MeOH in DCM)

ORD record

ord-231f0adc06904323a3f45894adfd1a8c

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376441B2