Dimethylformamide → (S)-ethyl 2-tert-butoxy-2-(6-cyano-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate

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Reaktionsgleichung

[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[C:20]([F:23])[C:19]2[C:14](=[CH:15][CH:16]=[C:17](Cl)[CH:18]=2)[C:13]=1[OH:25])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].[CH3:31][N:32](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[C:20]([F:23])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:31]#[N:32])[CH:18]=2)[C:13]=1[OH:25])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Komponenten

Reaktionsbedingungen

Temperatur: 100 °C

Versuchsvorschrift

A mixture of (S)-ethyl 2-tert-butoxy-2-(6-chloro-4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate (0.2186 g, 0.593 mmol), zinc(II) cyanide (0.0695 g, 0.593 mmol), XPhos Palladacycle (0.044 g, 0.0593 mmol) and sodium bicarbonate (0.005 g, 0.0593 mmol) in anhydrous DMF (3.0 mL) was heated in a microwave at 100° C. for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate (2×). The Combined organic layer was washed with 5% lithium chloride solution, brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 15% ethyl acetate/hexanes) to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C20H21FNO4: 358.2. Found: 357.9.

Aufarbeitung

extractionextracted with ethyl acetate (2×)
washThe Combined organic layer was washed with 5% lithium chloride solution, brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
custompurified by flash column chromatography (silica gel, 0 to 15% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag: ord-08fec636aa0e4ad893de26e4626257ab
Quelldatensatz: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09284323B2

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