tert-Butyl methyl ether → 2,5-difluoro-4-nitrobenzonitrile

HRID 715507Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[F:12].[C:13]([Cu])#[N:14].[O-]S([O-])(=O)=O.[Na+].[Na+].CC(OC)(C)C>CN1C(=O)CCC1>[F:12][C:3]1[CH:4]=[C:5]([N+:9]([O-:11])=[O:10])[C:6]([F:8])=[CH:7][C:2]=1[C:13]#[N:14]

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 1-bromo-2,5-difluoro-4-nitro-benzene (95 g, 399 mmol) and CuCN (71.8 g, 798 mmol) in NMP (700 mL) was set to a pre-heated 160° C. oil-base and stirred at 160° C. under N2 over 450 min. The mixture was cooled to RT, charged with Na2SO4 (300 g) and MTBE (1 L), and stirred for an additional 15 min. The resulting mixture was filtered and the filtrate was charged with 800 mL of water, then the separated aqueous layer was extracted with MTBE. The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated. The material was recrystallized from EtOH/water (2/1) to yield 2,5-Difluoro-4-nitro-benzonitrile (50 g, 68% yield) as a pale brown solid. 1H NMR (400 MHz, CDCl3) δ 7.96-7.95 (dd, 1H), 7.67-7.64 (dd, 1H).

Workup

customwas set to a pre-heated 160° C.
temperatureThe mixture was cooled to RT
stirringstirred for an additional 15 min
filtrationThe resulting mixture was filtered
additionthe filtrate was charged with 800 mL of water
extractionthe separated aqueous layer was extracted with MTBE
washThe combined organic layers were washed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe material was recrystallized from EtOH/water (2/1)

Sources & evidence

ORD record: ord-6ebed485f2de4aaf87cb9cdd1799a2fc
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187464B2

Reaction notes

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