Acetic Acid → N-[(3-chlorobiphenyl-4-yl)methyl]cyclopropanamine

HRID 631023Notes

Reaction equation

HRID 631023 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.C(O)(=O)C.[Cl:9][C:10]1[CH:11]=[C:12]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:13]=[CH:14][C:15]=1[CH:16]=O.C([BH3-])#N.[Na+]>CO.CCCCCCC.C(OCC)(=O)C>[Cl:9][C:10]1[CH:11]=[C:12]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:13]=[CH:14][C:15]=1[CH2:16][NH:4][CH:1]1[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 214412843-Chloro-biphenyl-4-carboxaldehyde

Product 1

HCID 67071683N-[(3-chlorobiphenyl-4-yl)methyl]cyclopropanamineYield 84.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

To a cooled solution of 1.82 ml (26 mmol) of cyclopropylamine and 1.90 ml (33 mmol) of acetic acid, together with 3 g of 3 Å molecular sieves, in 45 ml of methanol, are added 2.85 g (13.1 mmol) of 3-chlorobiphenyl-4-carbaldehyde. The reaction mixture is stirred for 4 hrs at reflux. The reaction mixture is then cooled to ambient temperature and 1.24 g (19.7 mmol) of sodium cyanoborohydride are slowly added. The reaction mixture is further stirred for 2 hrs at reflux. The solvent is removed under vacuum and 100 ml of water are then added to the residue and the pH is adjusted to 10 with sodium hydroxyde. The watery layer is extracted three times with dichloromethane (3×50 ml); the combined organic layers are filtered over a phase separator filter to yield after concentration 11.61 g of a yellow oil. Column chromatography (gradient heptane/ethyl acetate) yielded 2.84 g (79% yield) of N-[(3-chlorobiphenyl-4-yl)methyl]cyclopropanamine as a colourless oil (M+H=258).

Workup

  1. temperatureat reflux
  2. stirringThe reaction mixture is further stirred for 2 hrs
  3. temperatureat reflux
  4. customThe solvent is removed under vacuum and 100 ml of water
  5. additionare then added to the residue
  6. extractionThe watery layer is extracted three times with dichloromethane (3×50 ml)
  7. filtrationthe combined organic layers are filtered over a phase separator
  8. filtrationfilter
  9. customto yield after concentration 11.61 g of a yellow oil

Sources & evidence

ORD record
ord-4dddaf2f367e4e16a35db27b02ff8404
Source dataset
uspto-grants-2016_04
Patent number
US09320277B2

Reaction notes

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