Diisopropylamine → 2-(Pent-1-ynyl)pyridine

Temperature

85 °C

To a degassed solution of 2-iodopyridine (0.519 mL, 4.88 mmol), bis(triphenylphosphine)palladium(II) chloride (0.205 g, 0.293 mmol), copper(I) iodide (0.046 g, 0.244 mmol), and diisopropylamine (2.78 mL, 19.5 mmol) in N,N-dimethylformamide (20 mL) was added 1-pentyne (0.721 mL, 7.32 mmol). The reaction was heated to 85° C. for 3 hrs. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (150 mL), washed with a 10% aqueous solution of lithium chloride (2×100 mL), washed with a 2M aqueous solution of ammonium hydroxide (100 mL), washed with brine (100 mL), and dried over anhydrous sodium sulfate. Concentration followed by purification by silica gel chromatography with hexanes/ethyl acetate (3/2) afforded 2-(pent-1-ynyl)pyridine (636 mg, 4.31 mmol). The compound had an HPLC retention time=0.982 min.—Column: YMC S5 COMBISCREEN® 4.6×50 mm; Gradient time: 4 min; Flow rate=4 ml/min; Solvent A=10% MeOH—90% Water—0.2% H3PO4; Solvent B=90% MeOH—10% water—0.2% H3PO4; Start % B=0; Final % B=100. LC-MS: M+1=146.3. 1H NMR (400 MHz, CDCl3) δ ppm 1.06 (t, 3H), 1.67 (dt, J=7.23 Hz, 2H), 2.43 (t, J=7.15 Hz, 2H), 7.18 (ddd, J=7.65, 4.89, 1.00 Hz, 1H), 7.38 (d, J=7.78 Hz, 1H), 7.62 (td, J=7.72, 1.88 Hz, 1H), and 8.55 (d, J=4.27 Hz, 1H).

1. temperatureThe reaction mixture was cooled to room temperature
2. washwashed with a 10% aqueous solution of lithium chloride (2×100 mL)
3. washwashed with a 2M aqueous solution of ammonium hydroxide (100 mL)
4. washwashed with brine (100 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationConcentration
7. customfollowed by purification by silica gel chromatography with hexanes/ethyl acetate (3/2)

ORD record

ord-6633a99ef664412c8d776a96ea05bda4

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404672B2