Ammonium Chloride → 5-fluoro-1H-indole-7-carbaldehyde

Temperature

-78 °C

Add vinylmagnesium bromide (1 M in tetrahydrofuran, 85.2 mL, 85.2 mmol) dropwise to a solution of 2-dibutoxymethyl-4-fluoro-1-nitro-benzene (8.5 g, 28.4 mmol) in tetrahydrofuran (250 mL) at −78° C. Warm the reaction mixture −45° C. to −50° C. for 30 minutes, cool to −78° C., and add vinylmagnesium bromide (1 M in tetrahydrofuran, 85.2 mL, 85.2 mmol) dropwise. Warm the reaction mixture to −45° C. to −50° C. for 20 minutes, then add saturated aqueous ammonium chloride (300 mL). Warm the mixture to room temperature and extract with diethyl ether (200 mL×2). Wash the combined organic phases with saturated aqueous sodium chloride (400 mL×2), dry over sodium sulfate, and concentrate under reduced pressure. Dissolve the residue in tetrahydrofuran (100 mL), add 0.5 N HCl (10 mL), and stir for 20 minutes. Dilute the mixture with diethyl ether (200 mL), wash sequentially with saturated aqueous sodium bicarbonate (200 mL×3) and saturated aqueous sodium chloride (200 mL×2). Dry the organic phase over sodium sulfate and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with 5% to 10% ethyl acetate in hexanes to provide the desired compound as a pale yellow solid (2.6 g, 56%).

1. temperatureWarm the reaction mixture −45° C. to −50° C. for 30 minutes
2. temperatureWarm the reaction mixture to −45° C. to −50° C. for 20 minutes
3. temperatureWarm the mixture to room temperature
4. extractionextract with diethyl ether (200 mL×2)
5. washWash the combined organic phases with saturated aqueous sodium chloride (400 mL×2)
6. dry with materialdry over sodium sulfate
7. concentrationconcentrate under reduced pressure
8. dissolutionDissolve the residue in tetrahydrofuran (100 mL)
9. additionadd 0.5 N HCl (10 mL)
10. additionDilute the mixture with diethyl ether (200 mL)
11. washwash sequentially with saturated aqueous sodium bicarbonate (200 mL×3) and saturated aqueous sodium chloride (200 mL×2)
12. dry with materialDry the organic phase over sodium sulfate
13. concentrationconcentrate under reduced pressure
14. washeluting with 5% to 10% ethyl acetate in hexanes

ORD record

ord-81bfde49081347f98174861c29ee10f9

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08648063B2