Chlorosulfonic acid → 4-(4-Cyano-2-Methoxyphenyl)-6-Fluoro-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonyl Chloride

HRID 528610

Reaktionsgleichung

[F:1][C:2]1[CH:21]=[CH:20][C:5]2[O:6][CH2:7][CH2:8][N:9]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=3[O:18][CH3:19])[C:4]=2[CH:3]=1.[Cl:22][S:23](O)(=[O:25])=[O:24]>C(Cl)Cl>[C:14]([C:13]1[CH:16]=[CH:17][C:10]([N:9]2[CH2:8][CH2:7][O:6][C:5]3[CH:20]=[C:21]([S:23]([Cl:22])(=[O:25])=[O:24])[C:2]([F:1])=[CH:3][C:4]2=3)=[C:11]([O:18][CH3:19])[CH:12]=1)#[N:15]

Komponenten

Reaktionsbedingungen

Temperatur: -78 °C

Versuchsvorschrift

To a vial charged with 4-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile (0.234 g, 0.823 mmol) was added DCM (3.29 ml). The resulting solution was cooled to −78° C. and chlorosulfonic acid (0.137 ml, 2.058 mmol) was added faster than dropwise. After 30 min the mixture was warmed to 0° C. and the mixture was allowed to stir and warm to rt over 3 hr. LC-MS indicated conversion to the desired product mass (M+23). The reaction mixture was added to ice carefully and EtOAc was used to wash reaction vial. The resulting mixture was extracted with EtOAc (2×). The layers were separated and the cloudy aqueous phase was diluted with brine and extracted once more with EtOAc. The combined organics were dried with Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified with a 40 g silicycle HP column ramping EtOAc in heptane (0-50%) providing product 4-(4-cyano-2-methoxyphenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (0.093 g, 0.243 mmol, 29.5% yield) as a light yellow solid. m/z (ESI) 405.2 (M+Na)+.

Aufarbeitung

temperatureAfter 30 min the mixture was warmed to 0° C.
temperaturewarm to rt over 3 hr

Quellen und Nachweise

ORD-Eintrag: ord-7ed94cec860345058a93a67c663114c8
Quelldatensatz: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09346798B2

Verknüpfte Notizen

Wird geladen…