Tetrabutylammonium Fluoride → HCID 59267834, compound

Temperature

80 °C

TBAF (1 M in THF) (0.9 mL, 0.9 mmol) was added to a solution of methyl 5-[(6-chloro-5-[1-(2-hydroxyethyl)-1H-indol-5-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl)oxy]-2-methylbenzoate (105 mg, 0.173 mmol) in THF (2 mL). The reaction was heated at 80° C. for 1 h. TBAF (1 M in THF) (0.2 mL, 0.2 mmol) was added and heating continuted for an additional 1 h. Volatiles were removed and the residue was dissolved in MeOH (3 mL) and treated with 2.5 N aqueous NaOH (1 mL). The mixture was stirred at 45° C. for 1.5 h, then at ambient temperature overnight. The reaction was diluted with EtOAc and the layers were separated. The organic layer was washed with 1 M aqueous HCl, water and brine, dried (Na2SO4), filtered, and concentrated. Chromatography over silica eluting with 8% MeOH/DCM containing AcOH (60 drops in 200 mL) afforded the title compound as an off-white solid. LC-MS: calculated for C25H20ClN3O4 461.90, observed m/e 462.3 (M+H)+ (Rt 1.77 min). 1H NMR (500 MHz, CD3OD): δ 7.86 (d, 1H), 7.55 (s, 1H), 7.47 (s, 1H), 7.46-7.36 (m, 3H), 7.34, (s, 1H), 7.27 (d, 1H), 7.19 (dd, 1H), 6.47 (d, 1H), 4.29 (t, 2H), 3.89 (t, 2 H), 2.61 (s, 3H).

1. temperatureheating
2. customVolatiles were removed
3. dissolutionthe residue was dissolved in MeOH (3 mL)
4. additiontreated with 2.5 N aqueous NaOH (1 mL)
5. customat ambient temperature
6. customovernight
7. additionThe reaction was diluted with EtOAc
8. customthe layers were separated
9. washThe organic layer was washed with 1 M aqueous HCl, water and brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. additionChromatography over silica eluting with 8% MeOH/DCM containing AcOH (60 drops in 200 mL)

ORD record

ord-1314adae322341cc97accc26bb54ac8d

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394969B2