Potassium Carbonate → (3R)-N-[4'-(Hydroxymethyl)-3'-fluoro-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide

Participants

Role	Name	HCID	Charge
Reactant	Potassium Carbonate	HCID 11430	—
Reactant	Sodium Hydroxide	HCID 14798	—
Reactant	Bis(pinacolato)diborane	HCID 2733548	—
Reactant	(4-Bromo-2-fluorophenyl)methanol	HCID 2734027	—
Reactant	(3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide	HCID 58742393	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(3R)-N-[4'-(Hydroxymethyl)-3'-fluoro-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide	HCID 58742400	—

Reaction Conditions

Temperature	85 °C

Reaction Steps

492 mg (1.62) of bis(pinacolato)diboron, 804 mg (5.82 mmol) of dry potassium carbonate, and 398 mg (1.94 mmol) of (4-bromo-2-fluorophenyl)methanol are dissolved in 4.2 ml of DMF. Argon is passed through the reaction mixture for 15 minutes, and then 59 mg (0.08 mmol) of PdCl2(dppf) are added, and the mixture is heated at 85° C. overnight. Then, 500 mg (1.62 mmol) of (3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide, 8.1 ml of 1N sodium hydroxide solution and a further 59 mg (0.02 mmol) of PdCl2(dppf) are added. The mixture is heated at 85° C. overnight. The solvent is removed under reduced pressure. The crude product is purified by preparative HPLC. 21 mg (3% of theory) of the title compound are obtained.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07138410B2
Source dataset	uspto-grants-2006_11
ORD ID	ord-f2b2e38ec9ee40f9b1f25029cf5227c9
Source note	uspto-grants-2006_11