Cesium carbonate → (1S,4S)-5-(2,6-dichloropyridin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane

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	(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrobromide	HCID 11159293	—
Reactant	2,6-Dichloro-4-iodopyridine	HCID 11737393	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	(1S,4S)-5-(2,6-dichloropyridin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane	HCID 117678389	44.1%

Reaction Conditions

Temperature	140 °C

Reaction Steps

To a microwave vial charged with 2,6-dichloro-4-iodopyridine (100 mg, 0.37 mmol), (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane (49.19 mg, 0.44 mmol) and cesium carbonate (66.29 mg, 0.48 mmol) in dioxane (5 mL) was added Pd2(dba)3 (3.5 mg, 0.048 mmol) and xantphos (3.5 mg, 0.048 mmol) under nitrogen. The vial was sealed and heated by microwave irradiation at 140° C. for 1 h. The reaction mixture was concentrated in vacuo, and resulting residue was purified by TLC (PE:EA=2:1) to afford (1S,4S)-5-(2,6-dichloropyridin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane (40 mg, 35% yield).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09266862B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-c6585c66399f4be59be5787cfab0457f
Source note	uspto-grants-2016_02