Ethyl Acetate → 4-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carbonitrile

HRID 1676400Notes

Reaction equation

Cl[C:2]1[C:3](=[O:15])[N:4]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[CH:5]=[CH:6][N:7]=1.CCOC(C)=O.[CH3:22][N:23]1CCCC1=O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2]>[F:14][C:11]1[CH:12]=[CH:13][C:8]([N:4]2[CH:5]=[CH:6][N:7]=[C:2]([C:22]#[N:23])[C:3]2=[O:15])=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-chloro-1-(4-fluorophenyl)pyrazin-2(1H)-one (1.0 g, 4.5 mmol), dppf (0.25 g, 0.45 mmol), Pd2(dba3) (0.20 g, 0.22 mmol) and Zn(CN)2 (0.31 g, 2.7 mmol) in N-methylpyrrolidone (20 mL) was heated at 120° C. for 15 hours in a sealed vial. The residue was cooled to room temperature, treated with EtOAc (300 mL), washed with a solution of saturated aq. NH4Cl, conc. NOH, water (72 mL, a ratio of 4:1:4) and brine, dried over MgSO4, and concentrated. The crude was purified by silica gel flash column chromatography (100% CH2Cl2) to afford 0.77 g (80%) of the desired product. LRMS (ESI pos) m/e 216.0 (M+1). 1H-NMR (400 MHz, CDCl3) δ 7.58 (d, 1H), 7.46 (d, 1H), 7.42 (m, 2H), 7.26 (m, 2H); 19F-NMR (376 MHz, CDCl3) δ −109.6.

Workup

temperatureThe residue was cooled to room temperature
washwashed with a solution of saturated aq. NH4Cl, conc. NOH, water (72 mL
dry with materiala ratio of 4:1:4) and brine, dried over MgSO4
concentrationconcentrated
customThe crude was purified by silica gel flash column chromatography (100% CH2Cl2)

Sources & evidence

ORD record: ord-391b395af7a241a5af362fb3e11081c7
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003662B2

Reaction notes

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