Ammonium Chloride → HCID 86649068, Verbindung

HRID 1424480Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1424480
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([O:14]CC)=O)[N:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([Mg]Br)=[CH:20][C:19]=1[O:26][CH3:27].CC1CCCO1.[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[C:19]([O:26][CH3:27])[CH:20]=2)=[O:14])[N:3]=1

Komponenten

5

Edukt 3

HCID 25517Ammonium ChlorideHCID 3477840Ethyl 4-chloroquinazoline-2-carboxylateHCID 178426731HCID 178426731, Verbindung2×

Produkt 1

HCID 86649068HCID 86649068, VerbindungAusbeute 62,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-35 °C

Versuchsvorschrift

To a stirred mixture of ethyl 4-chloroquinazoline-2-carboxylate (500 mg, 2.11 mmol) in THF (17 mL) at −40° C. was added dropwise 1 M 4-fluoro-3-methoxyphenylmagnesium bromide/2-methyltetrahydrofuran (2.53 mL, 2.53 mmol). The reaction mixture was stirred at −30 to −40° C. for 3 h. Additional 1 M 4-fluoro-3-methoxyphenylmagnesium bromide/2-methyltetrahydrofuran (1.05 mL, 1.05 mmol) was added and stirring was continued at −30 to −40° C. for an additional 1.5 h. To the mixture was added saturated aq ammonium chloride (25 mL) and the mixture was allowed to warm to rt. The mixture was extracted with EtOAc (2×) and the combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with diethyl ether and the resulting solid was collected by filtration and dried to afford (4-chloroquinazolin-2-yl)(4-fluoro-3-methoxyphenyl)methanone as a colorless solid (417 mg, 62%). 1H NMR (300 MHz, DMSO-d6) δ ppm 3.92 (s, 3H), 7.42 (dd, J=11.1, 8.7 Hz, 1H), 7.64 (m, 1H), 7.85 (d, J=8.4 Hz, 1H), 8.04 (m, 1H), 8.23-8.25 (m, 2H), 8.43 (d, J=8.4 Hz, 1H); LC-MS (ESI) m/z 317 (M+H)+.

Aufarbeitung

  1. stirringstirring
  2. waitwas continued at −30 to −40° C. for an additional 1.5 h
  3. temperatureto warm to rt
  4. extractionThe mixture was extracted with EtOAc (2×)
  5. dry with materialthe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated with diethyl ether
  9. filtrationthe resulting solid was collected by filtration
  10. customdried

Quellen und Nachweise

ORD-Eintrag
ord-fdd8e9cf5b5f4f37986a1d095171e0df
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08927711B2

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