Cesium carbonate → 2-Bromo-6-(7,7-difluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-fluorobenzyl Acetate

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-Dibromo-4-fluorobenzyl acetate	HCID 67016593	—
Reactant	7,7-Difluoro-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one	HCID 86683735	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	2-Bromo-6-(7,7-difluoro-1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-4-fluorobenzyl Acetate	HCID 86683736	62%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 1,4-dioxane (40 mL), 113o (890 mg, 3.94 mmol), 2,6-dibromo-4-fluorobenzyl acetate 101c (3847 mg, 11.8 mmol), Pd2(dba)3 (180 mg, 0.197 mmol), XantPhos (227 mg, 0.394 mmol), and cesium carbonate (2.57 g, 7.88 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 16 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 3:1 petroleum ether/ethyl acetate to afford 113p (1100 mg, 62%) as a white solid. MS-ESI: [M+H]+ 471.1.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08729072B2
Source dataset	uspto-grants-2014_05
ORD ID	ord-66c1e8bfb7154441b687fb2d91672fff
Source note	uspto-grants-2014_05