Sodium Sulfate → N-[(4-methoxyphenyl)methyl]cyclobutanamine

HRID 889454Notes

Reaction equation

HRID 889454 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[CH:11]1([NH2:15])[CH2:14][CH2:13][CH2:12]1.[O-]S([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>ClCCl.[OH-].[Na+].Cl([O-])(=O)(=O)=O.[Mg+2].Cl([O-])(=O)(=O)=O>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH:15][CH:11]2[CH2:14][CH2:13][CH2:12]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 24436Sodium SulfateHCID 312444-MethoxybenzaldehydeHCID 75645CyclobutylamineHCID 4311764Sodium borohydride

Product 1

HCID 59313984N-[(4-methoxyphenyl)methyl]cyclobutanamineYield 95.8%

Reagents, catalysts & solvents 3

HCID 24840Magnesium perchlorateCatalystHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

4-Methoxybenzaldehyde (5.63 mL, 46.4 mmol) and cyclobutanamine (3.3 g, 46.4 mmol) in dichloromethane (40 mL) were stirred at room temperature. After 45 min., magnesium perchlorate (0.231 g, 2.320 mmol) was added, and the reaction mixture was stirred at room temperature. After 16 hours, the reaction mixture was treated with Na2SO4 (2 g) and stirred at room temperature for 2 hours, filtered and concentrated to dryness. The reaction mixture was dissolved in methanol (40 mL), cooled to 0° C., and NaBH4 (1.6 g, 69.6 mmol) was added. After 15 min., the reaction mixture was warmed to room temperature. After 2 hours, the reaction mixture was diluted with 1N NaOH (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to isolate 4A (8.5 g, 82% yield) as a clear oil. HPLC: Rt=0.82 min (PHENOMENEX® Luna 5 micron C18 4.6×30 mm, 10-90% aqueous methanol containing 0.1% TFA, 2 min gradient, flow rate=5 mL/min, detection at 254 nm). MS (ES): m/z=192.6 [M+H]+.

Workup

  1. waitAfter 16 hours
  2. stirringstirred at room temperature for 2 hours
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. dissolutionThe reaction mixture was dissolved in methanol (40 mL)
  6. temperaturecooled to 0° C.
  7. waitAfter 15 min.
  8. temperaturethe reaction mixture was warmed to room temperature
  9. waitAfter 2 hours
  10. extractionextracted with ethyl acetate (3×100 mL)
  11. dry with materialThe combined organic layers were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-2f8ba0499ddc47018ec8122fd7fc370c
Source dataset
uspto-grants-2012_08
Patent number
US08252795B2

Reaction notes

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