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

Participants

Role	Name	HCID	Charge
Reactant	Toluene	HCID 1140	—
Reactant	N-[(1S)-1-(4-bromophenyl)ethyl]cyclopropanecarboxamide	HCID 800360	—
Reactant	Sodium t-butoxide	HCID 23676156	—
Reactant	3-[3,5-Bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidine	HCID 53262186	—
Catalyst	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Catalyst	Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)	HCID 11029508	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	N-[(1S)-1-(4-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl)phenyl)-ethyl]cyclopropanecarboxamide	HCID 53261930	100%

Reaction Steps

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

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08536201B2
Source dataset	uspto-grants-2013_09
ORD ID	ord-f0e75c6ea85a4164a3dc0950d8405866
Source note	uspto-grants-2013_09