Acetic Acid → 1-(Diphenylmethyl)-N-methylazetidin-3-amine

HRID 1511804Notes

Reaction equation

HRID 1511804 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16](OS(C)(=O)=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.[CH3:23][NH2:24].CC(O)=O>CC(O)C>[CH:1]([N:14]1[CH2:17][CH:16]([NH:24][CH3:23])[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

5

Reactant 3

HCID 176Acetic AcidHCID 6329MethylamineHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 1

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

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester (commercial, 40 g, 126 mmol) in i-PrOH (440 mL) was added methylamine (41% in water, 320 mL). The mixture was heated in a 1.6 L-Parr reactor for 3.5 h at 75° C. (1.5-2 bar). After cooling to rt the solution was concentrated, diluted with water and extracted with DCM. The combined org. phases were washed with brine, dried over MgSO4 and concentrated. The residue was suspended in TBME (150 mL) and treated with AcOH (7.28 mL, 126 mmol). The mixture was stirred for 1 h at rt and the resulting crystals were filtered, washed with TBME and dried under HV to afford the title intermediate as its AcOH salt (15.07 g, 38%).

Workup

  1. temperatureAfter cooling to rt the solution
  2. concentrationwas concentrated
  3. additiondiluted with water
  4. extractionextracted with DCM
  5. washphases were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. filtrationthe resulting crystals were filtered
  9. washwashed with TBME
  10. customdried under HV

Sources & evidence

ORD record
ord-8b2388596a994f609df7b90fc00c60aa
Source dataset
uspto-grants-2012_07
Patent number
US08217029B2

Reaction notes

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