Iodine → N-Methyl-2-(thiophen-2-yl)ethan-1-amine

Temperature

7 °C

At 7° C., a solution of N-(2-(2-thienyl)ethyl)formamide (9.98 g, 63.8 mmol) in tetrahydrofuran (200 ml) was added to a suspension of sodium borohydride (2.89 g, 76.5 mmol) in tetrahydrofuran (200 ml). The mixture was stirred for 10 min. A solution of iodine (8.09 g, 31.9 mmol) in tetrahydrofuran (200 ml) was added dropwise. The reaction mixture was stirred for 30 min at 7° C. and 30 min at room temperature. It was heated to reflux for 16 h. The reaction mixture was cooled to 7° C. Methanol (500 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in 20% aqueous sodium hydroxide solution (500 ml) and tert-butyl methyl ether (200 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×200 ml). The combined organic layers were dried over magensium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (220 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent to give 2.82 g of N-methyl-N-(2-(2-thienyl)ethyl)amine.

1. stirringThe reaction mixture was stirred for 30 min at 7° C. and 30 min at room temperature
2. temperatureIt was heated
3. temperatureto reflux for 16 h
4. customThe solvent was removed in vacuo
5. dissolutionThe residue was dissolved in 20% aqueous sodium hydroxide solution (500 ml)
6. customThe phases were separated
7. extractionThe aqueous phase was extracted with tert-butyl methyl ether (2×200 ml)
8. dry with materialThe combined organic layers were dried over magensium sulfate
9. customThe solvent was removed in vacuo
10. customThe crude product was purified by flash chromatography on silica (220 g)

ORD record

ord-f4d94bd589144430838dab9e11e16064

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06127354