Methylamine → HCID 66652590, compound

HRID 572563Notes

Reaction equation

HRID 572563 reaction equation
[C:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1)(=O)[CH3:2].[CH3:12][NH2:13].[BH4-].[Na+].[OH-].[NH4+].C(=O)([O-])[O-].[K+].[K+].Br[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CCOC(C)=O>[C:8]([C:7]1[CH:10]=[CH:11][C:4]([CH:1]([N:13]([CH3:12])[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH3:2])=[CH:5][CH:6]=1)#[N:9]

Participants

10

Reactant 6

HCID 6329MethylamineHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 740444'-CyanoacetophenoneHCID 79177tert-Butyl bromoacetateHCID 4311764Sodium borohydride

Product 1

HCID 66652590HCID 66652590, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In THF (50 mL) was added 4-acetylbenzonitrile (5.0 g; 34 mmol), methylamine (21 mL; 2.00 M solution in THF; 42 mmol) and titanium isopropoxide (5.6 mL; 19 mmol). The mixture was stirred at RT overnight. Sodium borohydride (5.5 g; 145 mmol) was added and the reaction mixture was let stirred at RT for 2 h. Ammonium hydroxide solution 25% (100 mL) was added and the reaction mixture was stirred at RT for 1 h30. It was then filtered through a pad of celite, which was washed with EtOAc. The organic phase was washed with a saturated solution of NaHCO3, brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was then dissolved in CH3CN (41 mL). Potassium carbonate (10.3 g; 74 mmol) and tert-butyl bromoacetate (5.5 mL; 37 mmol) were added at RT and the reaction mixture was stirred at RT for 1 h30. EtOAc was added and the organic phase was washed with water and brine, dried over MgSO4, filtered and concentrated affording an oil which was purified by Flash Chromatography affording the title compound as a colorless oil. 1H NMR (DMSO-d6, 300 MHz) δ 7.79 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.2 Hz, 2H), 3.89 (q, J=6.7 Hz, 1H), 3.27 (d, J=16.7 Hz, 1H), 3.07 (d, J=16.7 Hz, 1H), 2.21 (s, 3H), 1.41 (s, 9H), 1.26 (d, J=6.8 Hz, 3H). LC/MS (Method B): 275.1 (M+H)+. HPLC (Method A) Rt 2.83 min (Purity: 96.8%).

Workup

  1. stirringthe reaction mixture was let stirred at RT for 2 h
  2. stirringthe reaction mixture was stirred at RT for 1 h30
  3. filtrationIt was then filtered through a pad of celite, which
  4. washwas washed with EtOAc
  5. washThe organic phase was washed with a saturated solution of NaHCO3, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe crude was then dissolved in CH3CN (41 mL)
  10. stirringthe reaction mixture was stirred at RT for 1 h30
  11. washthe organic phase was washed with water and brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customaffording an oil which
  16. customwas purified by Flash Chromatography

Sources & evidence

ORD record
ord-7b76564528234c189936bed23ca9714b
Source dataset
uspto-grants-2015_05
Patent number
US09029405B2

Reaction notes

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