Cesium carbonate → 2-Bromo-6-[6-(1-hydroxy-1-methyl-ethyl)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-benzaldehyde

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	2,6-Dibromobenzaldehyde	HCID 12648641	—
Reactant	6-(1-Hydroxy-1-methyl-ethyl)-3,4-dihydro-2H-isoquinolin-1-one	HCID 59216524	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	Water	HCID 962	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	2-Bromo-6-[6-(1-hydroxy-1-methyl-ethyl)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-benzaldehyde	HCID 86731002	—

Reaction Steps

To a mixture of 2,6-dibromo-benzaldehyde (1.60 g, 6.06 mmol), Pd2(dba)3 (222 mg, 0.243 mmol), xantphos (210 mg, 0.364 mmol), and Cs2CO3 (2.77 g, 8.49 mmol) in dioxane (60 ml) under argon was added 6-(1-hydroxy-1-methyl-ethyl)-3,4-dihydro-2H-isoquinolin-1-one (US2009/0306041) (995 mg, 4.85 mmol). The resulting mixture was refluxed overnight. After cooling down to r.t., water was added, and the mixture was extracted three times with EtOAc. The combined organic layers were dried, filtered, and evaporated to dryness. The crude product was purified by flash chromatography (silica gel, cyclohexane/EtOAC gradient) to yield Intermediate 42.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09233111B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-90af4d69beb0411eb58739cf642e7ca0
Source note	uspto-grants-2016_01