Benzyl Bromide → 2-(Benzyloxy)-6-chloro-3-nitropyridine

HRID 509395Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1(C)C=CC=CC=1.CCCCCC.CCOC(C)=O>[CH2:12]([O:8][C:6]1[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=[C:2]([Cl:1])[N:7]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a stirred mixture of 6-chloro-3-nitropyridin-2-ol (5 g, 0.0286 mol, Combi Blocks) in toluene (50.0 mL) in a 250 mL sealed tube, were added Ag2CO3 (11.84 g, 0.041 mol, Aldrich) and benzyl bromide (5.8 g, 0.033 mol) in one lot. The reaction mixture was capped, and the mixture was stirred for 12 h at 110° C. temperature. After completion of the reaction (monitored by TLC, 10% EtOAc in hexane), the reaction mixture was quenched with water (50 mL) and extracted with EtOAc (50 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a brown solid which was further purified column chromatography, silica gel (60-120 mesh) using 2-6% EtOAc in petroleum ether as an eluent to obtain the title compound as a white solid. 1H NMR (400 MHz, CDCl3) δ: 8.30 (d, J=8.1 Hz, 1H), 7.54 (d, J=6.9 Hz, 2H), 7.42-7.26 (m, 3H), 7.09 (t, J=8.4 Hz, 1H), 5.58 (s, 2H).

Workup

customsealed tube
customThe reaction mixture was capped
customthe reaction mixture was quenched with water (50 mL)
extractionextracted with EtOAc (50 mL×3)
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customto give a brown solid which

Sources & evidence

ORD record: ord-d4ca577526db4dbdb3ef2ae82d9a4841
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096527B2

Reaction notes

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