Sodium Iodide → HCID 23159968, compound

Temperature

0 °C

To a solution of 5-fluoro-2-propyl-1H-indole (0.17 g, 0.98 mmol) in N,N-dimethylformamide (6.2 mL) was added sodium hydride (60% in oil, 39 mg, 0.98 mmol) with stirring at 0° C., and the mixture was stirred at the same temperature for 10 min. Methyl 3-(4-([4-(chloromethyl)benzyl]oxy}phenyl)propanoate (0.31 g, 0.98 mmol) and sodium iodide (0.15 g, 0.98 mmol) were added to the obtained mixture and the mixture was stirred at room temperature for 17 hr. The reaction mixture was diluted with ethyl acetate, and the mixture washed with 5% aqueous potassium hydrogensulfate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give an oil. Then, a mixture of the obtained oil, 1 N aqueous sodium hydroxide solution (2.0 mL), methanol (5.0 mL) and tetrahydrofuran (10.0 mL) was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, and the mixture washed with 1 N hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC (gradient cycle A), and the object fractions were collected and concentrated. Water was added to the residue, and the mixture was adjusted to pH 7 with saturated aqueous sodium hydrogencarbonate, and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound (0.13 g, yield 31%) as colorless crystals. MS (APCI−): 444 (M−H).

1. stirringthe mixture was stirred at the same temperature for 10 min
2. stirringthe mixture was stirred at room temperature for 17 hr
3. washthe mixture washed with 5% aqueous potassium hydrogensulfate solution, water and saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customto give an oil
7. stirringwas stirred at room temperature for 2 hr
8. washthe mixture washed with 1 N hydrochloric acid and saturated brine
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by preparative HPLC (gradient cycle A), and the object fractions
12. customwere collected
13. concentrationconcentrated
14. additionWater was added to the residue
15. extractionextracted with ethyl acetate
16. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
17. concentrationconcentrated under reduced pressure

ORD record

ord-98c823b49bfc46209ac6a0c586a2252a

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07517910B2