Iodine → 4-Fluoro-N-methyl-benzenebutanamine

Temperature

70 °C

At 0° C., a solution of 4-(4-fluorophenyl)-N-methylbutyramide (1.30 g, 6.70 mmol) in THF (15 ml) was added dropwise to a suspension of sodium borohydride (604 mg, 16.0 mmol) in THF (15 ml). Successively, a solution of iodine (1.70 g, 6.70 mmol) in THF (20 ml) was added dropwise. The reaction mixture was heated to 70° C. for 16 hours. It was cooled to 0° C. Methanol (50 ml) was added carefully. The solvents were removed in vacuo. The residue was dissolved in a mixture of a 32% aqueous solution of sodium hydroxide (100 ml), water (50 ml), and tert-butyl methyl ether (200 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using a mixture of DCM/methanol/25% aqueous ammonia (first 100:10:1, then 100:20:2) as eluent, to give 180 mg of N-[4-(4-fluorophenyl)butyl]-N-methylamine.

1. temperatureIt was cooled to 0° C
2. customThe solvents were removed in vacuo
3. dissolutionThe residue was dissolved in a mixture of a 32% aqueous solution of sodium hydroxide (100 ml), water (50 ml), and tert-butyl methyl ether (200 ml)
4. customThe phases were separated
5. extractionThe aqueous phase was extracted with tert-butyl methyl ether (2×100 ml)
6. dry with materialThe combined organic layers were dried over magnesium sulphate
7. customThe solvent was removed in vacuo
8. customThe crude product was purified by flash chromatography on silica (80 g)
9. additiona mixture of DCM/methanol/25% aqueous ammonia (first 100:10:1

ORD record

ord-5086097aab7245d19e0db329b667b362

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06437147B1