Water → 5-Benzyl-6-(piperidin-4-yloxy)-isoquinoline

Participants

Role	Name	HCID	Charge
Reactant	Water	HCID 962	—
Reactant	Cesium carbonate	HCID 10796	—
Reactant	Potassium benzyltrifluoroboranuide	HCID 23692459	—
Reactant	4-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester	HCID 57646974	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	5-Benzyl-6-(piperidin-4-yloxy)-isoquinoline	HCID 57646939	5.5%

Reaction Steps

0.3 mL of water were added to a solution of 81 mg (0.2 mmol) of 4-(5-bromo-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester (11), 195 mg (0.6 mmol) of Cs2CO3, 14.6 mg (0.02 mmol) of Pd(dppf)Cl2 and 51 mg (0.26 mmol) of potassium benzyltrifluoroborate in 3 mL of THF. Argon was bubbled through the mixture for 10 minutes and then the reaction was heated to reflux for 16 h (incomplete conversion). After cooling to room temperature water and ethyl acetate were added. The organic layer was separated, dried over Na2SO4. After removal of the solvents 2 mL 5-6 N HCl in isopropanol was added. After 2 h the solvents were distilled off and the remainder was subjected twice to preparative HPLC to give 3.5 mg compound 29 as trifluoroacetate.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08501736B2
Source dataset	uspto-grants-2013_08
ORD ID	ord-4eaffa6cf9d543e0af084fba5a18e285
Source note	uspto-grants-2013_08