Ethyl Acetate → 2-[1-(2,5-Dichlorophenyl)-cyclopentyl]-acetamidine hydrochloride

HRID 2169248Notes

Reaction equation

HRID 2169248 reaction equation
[NH4+:1].[Cl-].C[Al](C)C.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[C:15]1([CH2:20][C:21]#[N:22])[CH2:19][CH2:18][CH2:17][CH2:16]1.C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC.C(Cl)(Cl)Cl>[ClH:7].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[C:15]1([CH2:20][C:21]([NH2:1])=[NH:22])[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 86725897[1-(2,5-Dichlorophenyl)-cyclopentyl]-acetonitrile

Product 1

HCID 867258982-[1-(2,5-Dichlorophenyl)-cyclopentyl]-acetamidine hydrochlorideYield 62.2%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 6212ChloroformSolventHCID 8058HexaneSolvent

Procedure

To a suspension of NH4Cl (1.939 g, 35.573 mmol) in toluene (30 mL) was added dropwise a solution of AlMe3 (2M in toluene; 9.48 mL, 18.972 mmol) at 0° C. and the mixture was stirred for 2 h at room temperature prior to the addition of a solution of [1-(2,5-dichlorophenyl)-cyclopentyl]-acetonitrile (202) in toluene (20 mL). It was then heated to 80° C. for 16 h. Silica thin layer chromatography was performed (40% ethyl acetate in hexane, Rf=0.1). The cooled reaction mixture was poured into a slurry of normal silica gel (100-200 mesh; 8 g) in CHCl3 (60 mL), followed by vigorous stirring for 30 min. The mixture was filtered off and the cake was rinsed with methanol. The combined filtrate was evaporated and the crude residue was taken in 10% methanol in dichloromethane (100 mL). The mixture was stirred for 30 min. The suspended solid was removed by filtration and the filtrate was evaporated. The crude product was triturated in diethylether and the solid was collected by filtration, dried under vacuum to afford 2-[1-(2,5-dichlorophenyl)-cyclopentyl]-acetamidine hydrochloride (203) (2.0 g, 62.2%) as a white solid.

Workup

  1. temperatureIt was then heated to 80° C. for 16 h
  2. customThe cooled reaction mixture
  3. stirringby vigorous stirring for 30 min
  4. filtrationThe mixture was filtered off
  5. washthe cake was rinsed with methanol
  6. customThe combined filtrate was evaporated
  7. stirringThe mixture was stirred for 30 min
  8. customThe suspended solid was removed by filtration
  9. customthe filtrate was evaporated
  10. customThe crude product was triturated in diethylether
  11. filtrationthe solid was collected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-1224def955ad47e1a4a6ad7d17c4679c
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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