Iodine → [4-(Trifluoromethyl)cyclohexyl]methanamine

Temperature

0 °C

At 0° C. a solution of 4-trifluoromethylcyclohexanecarboxylic acid amide (1.38 g, 7.07 mmol) in THF (20 ml) was added to a suspension of sodium borohydride (0.64 g, 16.97 mmol) in THF (20 ml). A solution of iodine (1.79 g, 7.07 mmol) in THF (20 ml) was added dropwise. The reaction mixture was heated to reflux for 16 hours. It was cooled to 0° C. Methanol (40 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in tert-butyl methyl ether (100 ml) and a 20% aqueous solution of sodium hydroxide. The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×70 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 (90 g), using DCM/methanol/25% aqueous ammonia (first 100:10:1; then 50:10:1) as eluent, to give 124 mg of ((4-trifluoromethylcyclohexyl)methyl)amine.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 16 hours
3. customThe solvent was removed in vacuo
4. dissolutionThe residue was dissolved in tert-butyl methyl ether (100 ml)
5. customThe phases were separated
6. extractionThe aqueous phase was extracted with tert-butyl methyl ether (2×70 ml)
7. dry with materialThe combined organic layers were dried over magnesium sulphate
8. customThe solvent was removed in vacuo
9. customThe crude product was purified by flash chromatography on silica (90 g)

ORD record

ord-a5d330b684c8404c8faec6c342aba7f6

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06437147B1