Benzophenone imine → (R)-3-[5-(Benzhydrylidene-amino)-2-fluoro-phenyl]-3-methyl-[1,4]oxazepan-5-one

Participants

Role	Name	HCID	Charge
Reactant	Benzophenone imine	HCID 136809	—
Reactant	Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane	HCID 11618717	—
Reactant	Sodium t-butoxide	HCID 23676156	—
Reactant	(R)-3-(5-bromo-2-fluoro-phenyl)-3-methyl-[1,4]oxazepan-5-one	HCID 58562938	—
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	Toluene	HCID 1140	—
Product	(R)-3-[5-(Benzhydrylidene-amino)-2-fluoro-phenyl]-3-methyl-[1,4]oxazepan-5-one	HCID 58563044	—

Reaction Conditions

Temperature	105 °C

Reaction Steps

Under an argon atmosphere a mixture of the crude (R)-3-(5-bromo-2-fluoro-phenyl)-3-methyl-[1,4]oxazepan-5-one (626 mg, 1.2 mmol), sodium tert-butoxide (356 mg, 3.59 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (52.4 mg, 0.12 mmol), tris(dibenzylideneacetone)-dipalladium(0) chloroform adduct (38.3 mg, 0.036 mmol), and benzophenonimine (447 mg, 2.4 mmol) in toluene (15 ml) was heated at 105° C. for 16 hours in a sealed vial. For the workup, the reaction mixture was cooled to room temperature, evaporated at reduced pressure, and purified by chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 10/20 as the eluent. (R)-3-[5-(Benzhydrylidene-amino)-2-fluoro-phenyl]-3-methyl-[1,4]oxazepan-5-one (intermediate C12A) was obtained as a light yellow foam (348 mg, 69% of theory). MS (ISP): m/z=403.3 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08673894B2
Source dataset	uspto-grants-2014_03
ORD ID	ord-324040da4b7345159e3e64a0893d390a
Source note	uspto-grants-2014_03