Hydrochloric Acid → 1-[3,5-Bis(trifluoromethyl)phenyl]ethan-1-amine--hydrogen chloride (1/1)

HRID 966968Notes

Reaction equation

HRID 966968 reaction equation
[ClH:1].CO[NH2:4].[F:5][C:6]([F:21])([F:20])[C:7]1[CH:8]=[C:9]([C:17](=O)[CH3:18])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1.C([O-])(=O)C.[Na+].[O-]S([O-])(=O)=O.[Mg+2].Cl>C(O)C.O>[ClH:1].[CH3:18][CH:17]([C:9]1[CH:8]=[C:7]([C:6]([F:21])([F:20])[F:5])[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=1)[NH2:4]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 1216161-(3,5-Bis(trifluoromethyl)phenyl)ethan-1-oneHCID 517045Sodium AcetateHCID 521874O-Methylhydroxylamine hydrochloride

Product 1

HCID 222935631-[3,5-Bis(trifluoromethyl)phenyl]ethan-1-amine--hydrogen chloride (1/1)Yield 100%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

O-Methylhydroxylamine hydrochloride (19.57 g, 234 mmol) was added to a solution of 1-[3,5-bis(trifluoromethyl)phenyl]ethanone (50 g, 195 mmol), and sodium acetate (31.9 g, 234 mmol) in ethanol (450 mL) and water (150 mL) and the mixture was heated under reflux for 18 hours. The mixture was cooled, water (1000 mL) was added and the mixture was extracted with diethyl ether. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL), cooled to 0° C. and borane-tetrahydrofuran complex (1M in tetrahydrofuran, 730 mL) was added. The mixture was heated under reflux for 18 hours, cooled and hydrochloric acid (5M, 500 mL) was added slowly. The tetrahydrofuran was evaporated under reduced pressure and the mixture was basified with aqueous sodium hydroxide (4M). The mixture was extracted with ether and the combined organic fractions were washed with aqueous sodium hydroxide (4M) and dried (MgSO4), and ethereal hydrogen chloride (400 mL, 400 mmol) was added. The solid was collected, washing with diethyl ether, and dried in vacuo to give (RS)-α-methyl-3,5-bis(trifluoromethyl)benzenemethanamine hydrochloride as a colorless solid (48.2 g, 100%). 1H NMR (400 MHz, CD3OD) δ 8.13 (2H, s), 8.07 (1H, s), 4.73 (1H, q, J 6.8 Hz), 3.31 (2H, d, J 1.4 Hz), and 1.69 (3H, d, J 6.8 Hz). m/z (ES+) 258 (M+1). A sample was suspended in aqueous sodium hydroxide (4M) and extracted with ether. The combined organic fractions were washed with aqueous sodium hydroxide (4M), dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.85 (2H, s), 7.76 (1H, s), 4.30 (1H, q, J 6.6 Hz), 1.74 (2H, br s), and 1.42 (3H, d, J 6.6 Hz). m/z (ES+) 258 (M+1).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 18 hours
  3. temperatureThe mixture was cooled
  4. extractionthe mixture was extracted with diethyl ether
  5. dry with materialThe combined organic fractions were dried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. dissolutionThe residue was dissolved in tetrahydrofuran (100 mL)
  8. additionborane-tetrahydrofuran complex (1M in tetrahydrofuran, 730 mL) was added
  9. temperatureThe mixture was heated
  10. temperatureunder reflux for 18 hours
  11. temperaturecooled
  12. additionhydrochloric acid (5M, 500 mL) was added slowly
  13. customThe tetrahydrofuran was evaporated under reduced pressure
  14. extractionThe mixture was extracted with ether
  15. washthe combined organic fractions were washed with aqueous sodium hydroxide (4M)
  16. additionwas added
  17. customThe solid was collected
  18. washwashing with diethyl ether
  19. customdried in vacuo

Sources & evidence

ORD record
ord-817e8c3a320843ad97280bc88e6f81c9
Source dataset
uspto-grants-2005_10
Patent number
US06953792B2

Reaction notes

Loading…