Thionyl Chloride → 2-Chloro-5-nitro-3-(trifluoromethyl)pyridine

HRID 1050126Notes

Reaction equation

[N+:1]([C:4]1[CH:5]=[C:6]([C:11]([F:14])([F:13])[F:12])[C:7](O)=[N:8][CH:9]=1)([O-:3])=[O:2].O=S(Cl)[Cl:17]>CN(C=O)C>[Cl:17][C:7]1[C:6]([C:11]([F:14])([F:13])[F:12])=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-nitro-3-(trifluoromethyl)pyridin-2-ol (9 g, 43.2 mmol) in SOCl2 (30 mL, 411 mmol) was added a catalytic amount of DMF (0.033 ml, 0.432 mmol). The mixture was stirred at 80° C. overnight. After LCMS analysis showed the starting material was consumed, the solvent was removed in vacuo. The residue was dissolved in H2O and extracted with EA. The organic layer was washed with aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated to give the crude product, which was purified by column chromatography (PE/EA=10/1) to yield a yellow oil of 2-chloro-5-nitro-3-(trifluoromethyl)pyridine (8.5 g, 34.7 mmol, 80% yield): 1H NMR (400 MHz, CD3OD) δ9.43 (d, J=2.8 Hz, 1H), 8.92 (d, J=2.4 Hz, 1H); ES-LCMS m/z: 225.2 (M+H).

Workup

customwas consumed
customthe solvent was removed in vacuo
dissolutionThe residue was dissolved in H2O
extractionextracted with EA
washThe organic layer was washed with aqueous NaHCO3 and brine
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated
customto give the crude product, which
customwas purified by column chromatography (PE/EA=10/1)

Sources & evidence

ORD record: ord-04402d675bf34ae3923aeed80de79cbc
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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