Triethylamine → tert-butyl (2R,5S)-2-[(2-aminopyridin-3-yl)ethynyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate

Participants

Role	Name	HCID	Charge
Reactant	Triethylamine	HCID 8471	—
Reactant	2-Amino-3-bromopyridine	HCID 817700	—
Reactant	Tert-butyl (2R,5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-ethynylmorpholine-4-carboxylate	HCID 86726312	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	HCID 178418476	HCID 178418476	—
Solvent	Acetonitrile	HCID 6342	—
Product	tert-butyl (2R,5S)-2-[(2-aminopyridin-3-yl)ethynyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate	HCID 86726311	—

Reaction Conditions

Temperature	60 °C

Reaction Steps

A solution of tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-ethynylmorpholine-4-carboxylate (1 eq) and 3-bromopyridin-2-amine (1.4 eq) in acetonitrile (0.1M) and triethylamine (25 eq) was flushed with nitrogen for 10 minutes. Then bis(triphenylphosphine)palladium(ii) chloride (0.1 eq) and copper(i) iodide (1.2 eq) were added and the mixture was flushed again with nitrogen for 10 minutes. The reaction mixture was stirred at 60° C. for 2 hours in the dark. It was concentrated to dryness and the residue was purified by automated SiO2 flash chromatography system using solvent gradient of 0% to 10% MeOH/CH2Cl2 to afford the desired compound.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09315475B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-46c83fafaec84219823ccf49b3d9f004
Source note	uspto-grants-2016_04