Methylamine → 1-(Diphenylmethyl)-N-methylazetidin-3-amine

HRID 1027866Notes

Reaction equation

HRID 1027866 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16](O)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(C)(=O)=O.[CH3:24][NH2:25]>N1C=CC=CC=1.CN(C=O)C>[CH:1]([N:14]1[CH2:17][CH:16]([NH:25][CH3:24])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 31297Methanesulfonyl chlorideHCID 3304481-(Diphenylmethyl)azetidin-3-ol

Product 1

HCID 503191-(Diphenylmethyl)-N-methylazetidin-3-amine

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 1-benzhydryl-azetidin-3-ol (15 g, 62.7 mmol) in pyridine (60 mL) was cooled to 0° C., treated with mesyl chloride (6.3 mL, 81 mmol) and stirred at room temperature for 3 hours. The mixture was partitioned between ether (300 mL) and H2O (150 mL). The ether layer was washed with H2O, washed with brine, dried (MgSO4), filtered and concentrated to provide a greenish solid. The solid (23.3 g) was mixed with methyl amine (40% in H2O, 90 mL) in DMF (60 mL), heated at 85° C. for 48 hours, cooled to room temperature, and partitioned between H2O (200 mL) and EtOAc (400 mL). The aqueous was extracted with additional EtOAc. The combined organics were extracted twice with 2 N HCl (200 mL). The combined 2M HCl layers were basified with NaOH (50%) and extracted with diethyl ether. The ether layer was washed with brine, dried (MgSO4), filtered, concentrated under reduced pressure and purified on a silica gel column eluting with NH4OH/MeOH/CH2Cl2 (0.4/4/96) to provide the title compound. NMR (CDCl3): δ 2.26 (s, 3H), 2.83 (t, J=6 Hz, 2H), 3.33 (m, 1H), 3.46 (t, J=6 Hz, 2H), 7.15-7.20 (m, 2H), 7.24-7.29 (m, 4H), 7.36-7.4 (m, 4H). MS (DCI-NH3) m/z 254 (M+H)+.

Workup

  1. customThe mixture was partitioned between ether (300 mL) and H2O (150 mL)
  2. washThe ether layer was washed with H2O
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto provide a greenish solid
  8. temperatureheated at 85° C. for 48 hours
  9. temperaturecooled to room temperature
  10. custompartitioned between H2O (200 mL) and EtOAc (400 mL)
  11. extractionThe aqueous was extracted with additional EtOAc
  12. extractionThe combined organics were extracted twice with 2 N HCl (200 mL)
  13. extractionextracted with diethyl ether
  14. washThe ether layer was washed with brine
  15. dry with materialdried (MgSO4)
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure
  18. custompurified on a silica gel column
  19. washeluting with NH4OH/MeOH/CH2Cl2 (0.4/4/96)

Sources & evidence

ORD record
ord-bda82caa82e34ef8ae1a5ab7d144481d
Source dataset
uspto-grants-2014_05
Patent number
US08735411B2

Reaction notes

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