Cesium carbonate → (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	(R)-(+)-4-Hydroxy-2-pyrrolidinone	HCID 185505	—
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	2-Bromo-5-iodotoluene	HCID 2735574	—
Catalyst	Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)	HCID 11029508	—
Solvent	Water	HCID 962	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	(R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one	HCID 66816684	38.1%

Reaction Conditions

Temperature	110 °C

Reaction Steps

A mixture of 2-bromo-5-iodotoluene (500 mg, 1.68 mmol), (R)-4-hydroxy-pyrrolidinone (204 mg, 2.02 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (58.5 mg, 0.101 mmol), tris(dibenzylideneacetone)-dipalladium(0)-chloroform adduct (35.0 mg, 0.034 mmol) and cesium carbonate (769 mg, 2.36 mmol) in 1,4-dioxane (degassed, 5 ml) was stirred at 110° C. overnight in a nitrogen stream. The reaction mixture was treated with H2O and extracted with AcOEt (×2). The organic layers were combined and sequentially washed with H2O and saturated brine, and then dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (n-hexane/AcOEt) to give (R)-1-(4-bromo-3-methyl-phenyl)-4-hydroxy-pyrrolidin-2-one as a pale brown solid (173 mg, 38%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09169254B2
Source dataset	uspto-grants-2015_10
ORD ID	ord-83cc438b785f4e858558a55f309b7fb2
Source note	uspto-grants-2015_10