Acetic Acid → N2-cyclopropyl-N1-methyl-N1-phenylpropane-1,2-diamine

HRID 77694Notes

Reaction equation

HRID 77694 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.C(O)(=O)C.[CH3:9][N:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:11][C:12](=O)[CH3:13].C([BH3-])#N.[Na+]>CO.CCCCCCC.C(OCC)(=O)C>[CH:1]1([NH:4][CH:12]([CH3:13])[CH2:11][N:10]([CH3:9])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 69828CyclopropylamineHCID 4586991-(N-methylanilino)propan-2-oneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 68557675N2-cyclopropyl-N1-methyl-N1-phenylpropane-1,2-diamineYield 55.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of 2.52 g (44 mmol) of cyclopropylamine and 3.3 g (55 mmol) of acetic acid, together with 10 g of 3 Å molecular sieves, in 100 ml of methanol, are added 3.6 g (22 mmol) of 1-[methyl(phenyl)amino]propan-2-one. The reaction mixture is stirred for 2.5 hrs at reflux. The reaction mixture is then cooled to 0° C. and 2.07 g (33 mmol) of sodium cyanoborohydride are slowly added and the reaction mixture is further stirred for 2 hrs at reflux. The cooled reaction mixture is then filtered over a cake of diatomaceous earth. The cake is washed twice by 80 ml of methanol and the combined methanolic extracts are concentrated under vacuum. 100 ml of water are then added to the residue and the pH is adjusted to 10 with a 0.5 N solution of sodium hydroxyde. The watery layer is extracted three times with ethyl acetate (3×50 ml). The combined organic layers are washed twice by brine and are filtered over a phase separator filter to yield after concentration 9.2 g of a yellow oil. Column chromatography (gradient heptane/ethyl acetate) yielded 2.5 g (50% yield) of N2-cyclopropyl-N1-methyl-N1-phenylpropane-1,2-diamine as a brown oil (M+H=205).

Workup

  1. temperatureat reflux
  2. stirringthe reaction mixture is further stirred for 2 hrs
  3. temperatureat reflux
  4. customThe cooled reaction mixture
  5. filtrationis then filtered over a cake of diatomaceous earth
  6. washThe cake is washed twice by 80 ml of methanol
  7. concentrationthe combined methanolic extracts are concentrated under vacuum
  8. addition100 ml of water are then added to the residue
  9. extractionThe watery layer is extracted three times with ethyl acetate (3×50 ml)
  10. washThe combined organic layers are washed twice by brine
  11. filtrationare filtered over a phase separator
  12. filtrationfilter
  13. customto yield after concentration 9.2 g of a yellow oil

Sources & evidence

ORD record
ord-cf4a28ae94a04101915889f7a5b3b289
Source dataset
uspto-grants-2014_09
Patent number
US08841332B2

Reaction notes

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