Toluene → N-[(1S)-1-(4-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl)phenyl)-ethyl]cyclopropanecarboxamide

HRID 42630

Reaction equation

HRID 42630 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]2[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[F:16][C:17]([F:38])([F:37])[C:18]1[CH:19]=[C:20]([C:28]2([C:33]([F:36])([F:35])[F:34])[CH2:32][CH2:31][NH:30][CH2:29]2)[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(OCC)(=O)C>[F:26][C:24]([F:25])([F:27])[C:22]1[CH:21]=[C:20]([C:28]2([C:33]([F:36])([F:34])[F:35])[CH2:32][CH2:31][N:30]([C:2]3[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11]([CH:13]4[CH2:15][CH2:14]4)=[O:12])[CH3:9])=[CH:4][CH:3]=3)[CH2:29]2)[CH:19]=[C:18]([C:17]([F:16])([F:37])[F:38])[CH:23]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 800360N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamideHCID 23676156Sodium t-butoxideHCID 532621863-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine

Product 1

HCID 53261930N-[(1S)-1-(4-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl)phenyl)-ethyl]cyclopropanecarboxamideYield 100%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a reaction vessel, N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamide (134 mg), 3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine (211 mg), sodium t-butoxide (96 mg), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (10 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (18 mg) and toluene (6 ml) were added, and reacted in a microwave reactor (Initiator™, manufactured by Biotage) for 10 minutes at 120° C. Upon the completion of the reaction, ethyl acetate was added and the precipitates were filtered by using silica gel. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography to obtain N-[(1S)-1-(4-{3-[3,5-bis-(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}phenyl)ethyl]cyclopropanecarboxamide (269 mg). 1H-NMR (CDCl3) as given in Table 2

Workup

  1. customreacted in a microwave reactor (Initiator™, manufactured by Biotage) for 10 minutes at 120° C
  2. additionwas added
  3. filtrationthe precipitates were filtered
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f0e75c6ea85a4164a3dc0950d8405866
Source dataset
uspto-grants-2013_09
Patent number
US08536201B2

Linked notes

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