Hydrazine → 1-(2-Chloro-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]phenyl}methanamine

HRID 1930519Notes

Reaction equation

HRID 1930519 reaction equation
CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[Cl:49][C:50]1[CH:51]=[C:52]([C:57]2([C:62]([F:65])([F:64])[F:63])[CH2:61][CH2:60][NH:59][CH2:58]2)[CH:53]=[C:54]([Cl:56])[CH:55]=1.[Cl:66][C:67]1[CH:84]=[C:83](I)[CH:82]=[CH:81][C:68]=1[CH2:69][N:70]1C(=O)C2C(=CC=CC=2)C1=O.NN>C1(C)C=CC=CC=1.C(OC)(C)(C)C.CO.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:66][C:67]1[CH:84]=[C:83]([N:59]2[CH2:60][CH2:61][C:57]([C:52]3[CH:51]=[C:50]([Cl:49])[CH:55]=[C:54]([Cl:56])[CH:53]=3)([C:62]([F:65])([F:64])[F:63])[CH2:58]2)[CH:82]=[CH:81][C:68]=1[CH2:69][NH2:70]

Participants

10

Reactant 5

HCID 9321HydrazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 582188803-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidineHCID 66719866N-[(2-chloro-4-iodophenyl)methyl]phthalimide

Product 1

HCID 453777791-(2-Chloro-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]phenyl}methanamineYield 20.1%

Reagents, catalysts & solvents 4

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
80 °C

Procedure

Sodium tert-butoxide (0.2 g), Tris(dibenzylidene acetone) dipalladium(0) (chloroform adduct) (0.03 g) and xantphos (0.05 g) was added to the solution of 3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (0.4 g) and 2-(2-chloro-4-iodobenzyl)-1H-isoindole-1,3-(2H)-dione (0.69 g) in toluene under argon atmosphere, and the mixture was heated with stirring at 80° C. for 3 hours. The reaction solution was diluted with t-butylmethylether and then washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled away under the reduced pressure to yield the crude product. The product was dissolved in methanol, to which was then added aqueous hydrazine (0.03 g), followed by the mixture heated to reflux for 12 hours. The reaction solution was diluted with t-butylmethylether and then washed with saturated saline. The organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield 1-{2-chloro-4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]phenyl}methanamine (0.12 g). 1H-NMR (CDCl3) δ: 2.47-2.54 (1H, m), 2.78-2.85 (1H, m), 3.46-3.49 (2H, m), 3.69-4.01 (4H, m), 6.47-6.50 (1H, m), 6.73-6.76 (1H, m), 7.25-7.35 (4H, m).

Workup

  1. temperaturethe mixture was heated
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled away under the reduced pressure
  5. customto yield the crude product
  6. temperatureheated
  7. temperatureto reflux for 12 hours
  8. washwashed with saturated saline
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. distillationThe solvent was distilled away under the reduced pressure
  11. customthe residue was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-1be7feebf70f4baf841db1c2c1559177
Source dataset
uspto-grants-2012_05
Patent number
US08188122B2

Reaction notes

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