Ethyl Acetate → 2-Fluoro-3-methoxy-4-nitrobenzonitrile

HRID 914202Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[C:3]=1[F:13].[CH3:14][N:15](C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C(OCC)(=O)C>CC(N(C)C)=O.[Pd].[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:13][C:3]1[C:4]([O:11][CH3:12])=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[C:14]#[N:15]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 1-Bromo-2-fluoro-3-methoxy-4-nitrobenzene (250 mg, 1 mmol) and zinc cyanide (70 mg, 0.6 mmol) were stirred in DMA (5 mL) and purged with nitrogen. The palladium catalyst, Pd2(dba)3 (92 mg, 0.1 mmol), and the ligand, Davephos (79 mg, 0.2 mmol), were added and the reaction mixture was stirred at 90° C. overnight. It was then cooled to rt., diluted to ethyl acetate, washed with brine. Organic dried, concentrated and purified by flash column (EtOAc/Hexane=1:20) to give 170 mg product (87%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.15 (s, 3H) 7.42 (dd, J=9.0, 6.2 Hz, 1H) 7.65 (dd, J=9.0, 1.9 Hz, 1H).

Workup

custompurged with nitrogen
temperatureIt was then cooled to rt
washwashed with brine
concentrationOrganic dried, concentrated
custompurified by flash column (EtOAc/Hexane=1:20)

Sources & evidence

ORD record: ord-ecf7fdda55034b4fafd34377b486264c
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026234B2

Reaction notes

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