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

HRID 1027866ノート

反応式

HRID 1027866 の反応式
[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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-bda82caa82e34ef8ae1a5ab7d144481d
出典データセット
uspto-grants-2014_05
特許番号
US08735411B2

反応ノート

読み込み中…