Dichloromethane → 5-Hexynyl-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochloride

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Triethylamine	HCID 8471	—
Reactant	1-Hexyne	HCID 12732	—
Reactant	(S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylate	HCID 10688713	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Catalyst	HCID 178418476	HCID 178418476	—
Product	5-Hexynyl-3-(2-(S)-azetidinylmethoxy)pyridine dihydrochloride	HCID 9861754	56%

Reaction Steps

To a solution of 5-bromo-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from Example 54b (180 mg, 0.48 mmol), bis(triphenylphosphine)palladium(II) chloride (7 mg, 0.05 mmol), copper (I) iodide (2 mg) and triethylamine (1.0 mL) in CH2Cl2 (3 mL) was added 1-hexyne (8.3 mL, 0.72 mmol). The mixture was refluxed overnight and cooled to room temperature. The solvent was removed, and the residue was chromatographed on a silica gel column, eluting with EtOAc:hexane 1:1 to afford the title compound (102 mg, 56% yield). MS (CI/NH3) m/z 379 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ0.96 (t, J=6.6 Hz, 3H), 1.43 (s, 9H), 1.46-1.69 (m, 4H), 2.20-2.40 (m, 2H), 2.44-2.56 (m, 2H), 3.83-3.92 (m, 2H), 4.06-4.15 (m, 1H), 4.26-4.38 (m, 1H), 4.45-4.57 (m, 1H), 7.34 (br s, 1H), 7.51-7.58 (m, 1H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US06127386
Source dataset	uspto-grants-2000_10
ORD ID	ord-30dd755167144441b8dc391ae2c9f35d
Source note	uspto-grants-2000_10