Dimethylformamide → Methyl 3-fluoro-4-(3-methoxyprop-1-ynyl)benzoate

HRID 72975

Reaktionsgleichung

Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[F:12].CN(C=O)C.C(N(CC)CC)C.[CH3:25][O:26][CH2:27][C:28]#[CH:29]>CCOC(C)=O.[Cu]I>[F:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[C:29]#[C:28][CH2:27][O:26][CH3:25])[C:6]([O:8][CH3:9])=[O:7]

Komponenten

Reaktionsbedingungen

Temperatur: 0 °C

Versuchsvorschrift

To a mixture of methyl 4-bromo-3-fluoro-benzoate (2.5 g, 10.7 mmol) and copper (I) iodide (204 mg, 1.07 mmol) and palladium dichlorobis(triphenylphosphine) complex (753 mg, 1.07 mmol) under an atmosphere of argon was added DMF (21 mL) and the reaction mixture was cooled to 0° C. Triethylamine (1.95 mL, 13.9 mmol) was added followed by 3-methoxyprop-1-yne (997 μL, 11.8 mmol) and the reaction mixture was stirred at 60° C. for 70 minutes. The reaction mixture was cooled, diluted with EtOAc and filtered over Celite®. The filtrate was washed sequentially with 1 M HCl, 10% NH4OH and brine. The organic layer was separated, dried and concentrated in vacuo and the resulting residue was purified by silica gel column chromatography using EtOAc-hexanes (10-100%) as eluent to give methyl 3-fluoro-4-(3-methoxyprop-1-ynyl)benzoate (1.45 g, 61%). ESI-MS m/z calc. 222.2. Found 223.2 (M+1)+; Retention time: 1.53 minutes (3 min run); 1H NMR (400 MHz, CDCl3) δ 7.75 (ddd, J=11.2, 8.8, 1.5 Hz, 2H), 7.50 (dd, J=7.9, 7.0 Hz, 1H), 4.37 (s, 2H), 3.92 (s, 3H), 3.47 (s, 3H).

Aufarbeitung

temperatureThe reaction mixture was cooled
filtrationfiltered over Celite®
washThe filtrate was washed sequentially with 1 M HCl, 10% NH4OH and brine
customThe organic layer was separated
customdried
concentrationconcentrated in vacuo
customthe resulting residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag: ord-10236de4febe4584a00b5693ec8b01d3
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08828996B2

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