1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 3,3-Difluoro-4-[8-(2,3,4-trifluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Role	Name	HCID	Charge
Reactant	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
Reactant	Phenolate Sodium	HCID 4445035	—
Reactant	tert-Butyl 4-amino-3,3-difluoropiperidine-1-carboxylate	HCID 56932105	—
Reactant	HCID 67342605	HCID 67342605	—
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	1,4-Dioxane	HCID 31275	—
Product	3,3-Difluoro-4-[8-(2,3,4-trifluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester	HCID 67342863	—

Reaction Conditions

Temperature	160 °C

Reaction Steps

Through a suspension of 4-amino-3,3-difluoro-piperidine-1-carboxylic acid tert-butyl ester (90 mg, 381 μmol), 2-bromo-8-(2,3,4-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (prepared in analogy to example 66a-d, 162 mg, 495 μmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (15.8 mg, 15.2 μmol), sodium phenoxide (65.2 mg, 533 μmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (17.6 mg, 30.5 μmol) in dry dioxane (5.0 mL) was bubbled argon for 5 minutes, then heated to 160° C. in the microwave for 60 minutes. The catalyst was filtered off, washed with CH2Cl2 and the solvents evaporated. The residue was purified by flash chromatography (silica gel, 70 g, 0% to 100% EtOAc in heptane). The title compound was obtained as orange solid (27 mg, 15%).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08486967B2
Source dataset	uspto-grants-2013_07
ORD ID	ord-f989cf8297714e67a8f2f76e7f45a5f3
Source note	uspto-grants-2013_07