Sodium hydride → 2-Chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine

HRID 1050850Notes

Reaction equation

[H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][N:5]=1.[Cl:11][C:12]1[C:13](F)=[CH:14][C:15]([F:21])=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1>CN(C=O)C.CCOC(C)=O>[Cl:3][C:4]1[CH:9]=[C:8]([O:10][C:13]2[CH:14]=[C:15]([F:21])[C:16]([N+:18]([O-:20])=[O:19])=[CH:17][C:12]=2[Cl:11])[CH:7]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of sodium hydride (60% in mineral oil) (0.620 g, 15.5 mmol) in dry DMF (30 mL) under argon was treated portion wise with 2-chloro-4-hydroxypyridine (1.34 g, 10.3 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min, and then slowly warmed to RT. A solution of 5-chloro-2,4-difluoronitrobenzene (2 g, 10.3 mmol) in DMF (4.4 mL) was added to the suspension, and the mixture was heated at 90° C. for 15 h under argon. The mixture was cooled to RT, diluted with EtOAc (100 mL), washed with 10% aq LiCl (3×100 mL) and brine (2×100 mL), dried (MgSO4), concentrated to dryness, and purified by silica gel chromatography (EtOAc/hexanes) to yield 2-chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine as a bright yellow oil (1.42 g, 45% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.56 (dd, 1 H), 8.35 (dd, 1 H), 7.88 (dd, 1 H), 7.32 (dd, 1 H), 7.18 (m, 1 H); MS (ESI) m/z: 303.0 (M+H+).

Workup

temperatureslowly warmed to RT
temperaturethe mixture was heated at 90° C. for 15 h under argon
temperatureThe mixture was cooled to RT
washwashed with 10% aq LiCl (3×100 mL) and brine (2×100 mL)
dry with materialdried (MgSO4)
concentrationconcentrated to dryness
custompurified by silica gel chromatography (EtOAc/hexanes)

Sources & evidence

ORD record: ord-8028b2b0b40b4556bf544be0274acff7
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09387202B2

Reaction notes

Loading…