6-Bromo-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-one → [2-(4-Methoxy-benzyl)-1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl]-acetic Acid Tert-Butyl Ester

Participants

Role	Name	HCID	Charge
Reactant	6-Bromo-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-one	HCID 59216481	—
Reactant	HCID 178451183	HCID 178451183	—
Catalyst	(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium	HCID 6505921	—
Catalyst	Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzene	HCID 129828017	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	[2-(4-Methoxy-benzyl)-1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl]-acetic Acid Tert-Butyl Ester	HCID 59216409	—

Reaction Steps

6-Bromo-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-one (1.9 g, 5.5 mmole), Q-phos (0.0632 g, 0.11 mmole) and Pd(dba)2 (0.0781 g, 0.11 mmole) in 10 ml THF were added to 2-tert-butoxy-2-oxoethylzinc chloride 15 ml (0.55 M) under argon. The reaction mixture was stirred at room temperature for 16 hours. Next a third of the initial amount of Q-phos, Pd(dba)2 and zinc enolate were added and the mixture heated for 1 hour at 70° C. to bring the reaction to completion. 2 g of [2-(4-Methoxy-benzyl)-1-oxo-1,2,3,4-tetrahydro-isoquinolin-6-yl]-acetic acid tert-butyl ester was isolated by flash chromatography using silica gel column chromatography with 10%-40% ethyl acetate in hexane as eluent.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07683064B2
Source dataset	uspto-grants-2010_03
ORD ID	ord-f2aee4a1f9bc4de59de027b22477706a
Source note	uspto-grants-2010_03