Ethyl Acetate → 3-((2-Chloropyridin-4-yl)oxy)-2-ethyl-6-nitropyridine

HRID 718174Notes

Reaction equation

Br[C:2]1[C:3]([CH2:11][CH3:12])=[N:4][C:5]([N+:8]([O-:10])=[O:9])=[CH:6][CH:7]=1.[Cl:13][C:14]1[CH:19]=[C:18]([OH:20])[CH:17]=[CH:16][N:15]=1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>CC(N(C)C)=O>[Cl:13][C:14]1[CH:19]=[C:18]([O:20][C:2]2[C:3]([CH2:11][CH3:12])=[N:4][C:5]([N+:8]([O-:10])=[O:9])=[CH:6][CH:7]=2)[CH:17]=[CH:16][N:15]=1

Participants

Conditions

Temperature: 110 °C

Procedure

3-Bromo-2-ethyl-6-nitropyridine (2.6 g, 11.3 mmol) and 2-chloro-4-hydroxypyridine (2.9 g, 22.5 mmol) were dissolved in DMA (20 mL). The solution was sonicated and sparged with Ar for 10 min. K2CO3 (4.7 g, 33.8 mmol) was added and the reaction mixture was stirred at 110° C. for 12 h. EtOAc (80 mL) was added and the suspension was washed with 10% K2CO3 (aq) (2×50 mL), 5% LiCl (aq) (2×50 mL), and brine (2×50 mL). The solution was dried (Na2SO4), concentrated in vacuo, and the resultant residue was purified by silica gel chromatography (EtOAc/hexanes) to afford 3-((2-chloropyridin-4-yl)oxy)-2-ethyl-6-nitropyridine (1.3 g, 37.2%) as a yellow oil. 1H NMR (400 MHz, DMSO-d6): δ 8.38 (d, J=5.7 Hz, 1H), 8.25 (d, J=8.7 Hz, 1H), 7.96 (d, J=8.7 Hz, 1H), 7.82 (d, J=8.6 Hz, 1H), 7.16 (dd, J=5.7, 2.3 Hz, 1H), 2.79 (q, J=7.5 Hz, 2H), 1.21 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 280.0 (M+H+).

Workup

customThe solution was sonicated
customsparged with Ar for 10 min
washthe suspension was washed with 10% K2CO3 (aq) (2×50 mL), 5% LiCl (aq) (2×50 mL), and brine (2×50 mL)
dry with materialThe solution was dried (Na2SO4)
concentrationconcentrated in vacuo
customthe resultant residue was purified by silica gel chromatography (EtOAc/hexanes)

Sources & evidence

ORD record: ord-80804b49ebae47f68560a677484e00d9
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193719B2

Reaction notes

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