Chloroacetonitrile → 2-(5-Bromo-2-chloropyridin-3-yloxy)acetonitrile

HRID 2077590Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([OH:9])[C:5]([Cl:8])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:17][C:18]#[N:19]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:17][C:18]#[N:19])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A dry 10 mL, one neck round bottom flask was charged with 5-bromo-2-chloropyridin-3-ol (0.0518 g, 0.249 mmol), cesium carbonate (0.0972 g, 0.298 mmol), a stirbar and 2 mL dry DMF. The stirring slurry was treated with 2-chloroacetonitrile (0.0709 ml, 1.12 mmol) and fitted with an inert atmosphere inlet. The reaction was heated to 80° C. using an oil bath for 3 h, and cooled. The slurry was filtered through a 0.22 μm PTFE filter, and concentrated in vacuo. The residue was purified in one injection using a YMC pack diol-120-NP column (PN DN12S05-2520 wt, 250×20 mm, spherical particle, 5 μm particle size, 120 Å pore size, flow=20 mL/min: A=hexanes; B=THF; 15% B isocratic). A fraction that eluted from 10.0 to 11.8 minutes was isolated. The solvent was removed in vacuo to afford 2-(5-bromo-2-chloropyridin-3-yloxy)acetonitrile (0.0375 g, 61.0% yield). 1H NMR (300 MHz, chloroform-d) δ ppm 4.88 (s, 2H) 7.52 (d, J=1.97 Hz, 1H) 8.25 (d, J=1.97 Hz, 1H). 13C NMR (75 MHz, chloroform-d) δ ppm 54.71 (s, 1 C) 113.51 (s, 1 C) 118.90 (s, 1 C) 125.53 (s, 1 C) 140.63 (s, 1 C) 144.40 (s, 1 C) 148.93 (s, 1 C).

Workup

customfitted with an inert atmosphere inlet
customfor 3 h
temperaturecooled
filtrationThe slurry was filtered through a 0.22 μm PTFE
filtrationfilter
concentrationconcentrated in vacuo
customThe residue was purified in one injection
washA fraction that eluted from 10.0 to 11.8 minutes
customwas isolated
customThe solvent was removed in vacuo

Sources & evidence

ORD record: ord-a8c0c00ae3e74257b1c198a667612f76
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07928140B2

Reaction notes

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