Sodium Carbonate → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[3-(trifluoromethoxy)phenyl]-1-benzofuran-2-carboxamide hydrochloride

Participants

Role	Name	HCID	Charge
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	3-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)	HCID 2734385	—
Reactant	N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide hydrochloride	HCID 67313982	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dimethylformamide	HCID 6228	—
Product	N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-7-[3-(trifluoromethoxy)phenyl]-1-benzofuran-2-carboxamide hydrochloride	HCID 67314318	—

Reaction Conditions

Temperature	70 °C

Reaction Steps

200 mg (0.52 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide hydrochloride (Example 30A) and 106.8 mg (0.52 mmol) of 3-(trifluoromethoxy)phenylboronic acid are introduced into 2.0 ml of DMF. Addition of 0.78 ml of 2 M sodium carbonate solution and 21.2 mg (0.03 mmol) of PdCl2(dppf) is followed by heating at 70° C. for 17 h. After cooling, the reaction mixture is filtered through kieselguhr and purified by preparative HPLC. The product fractions are combined and concentrated and, after addition of a 5:1 mixture of methanol and 1N hydrochloric acid, again concentrated. Drying under high vacuum results in 48.8 mg (20% of theory) of the title compound.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07977485B2
Source dataset	uspto-grants-2011_07
ORD ID	ord-86d8f4c39c6f4e10a6cbb785de5dda57
Source note	uspto-grants-2011_07