Hydrochloric Acid → HCID 86715519, Verbindung

HRID 2284605Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2284605
[Br:1][C:2]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([CH3:21])[CH:15]=2)=[N:12][C:5]2[O:6][CH2:7][C:8](=O)[N:9]([CH3:10])[C:4]=2[CH:3]=1.B.C1COCC1.Cl>C1COCC1>[Br:1][C:2]1[C:13]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[C:16]([CH3:21])[CH:15]=2)=[N:12][C:5]2[O:6][CH2:7][CH2:8][N:9]([CH3:10])[C:4]=2[CH:3]=1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 86715520HCID 86715520, Verbindung

Produkt 1

HCID 86715519HCID 86715519, VerbindungAusbeute 78,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To the stirring solution of 7-bromo-6-(4-fluoro-3-methylphenyl)-1-methyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (595 mg) and THF (15 mL) under argon was added BH3.THF (5.1 mL, 1N solution in THF) dropwise for 20 min. After 12 h, the reaction mixture was cooled in ice-bath and transferred 1N aq. HCl (16 mL). Subsequently, cooling bath was removed and heated at 80° C. for 1 h. The reaction mixture was concentrated, basified with aq. NaHCO3 solution and extracted with EtOAc (2×125 mL). Workup of the combined organic layers followed by flash column chromatographic purification (Combiflash® companion System® with RediSep® silica gel column 24 g and 30-50% EtOAc/hexanes eluting solvent) provided 450 mg of 7-bromo-6-(4-fluoro-3-methylphenyl)-1-methyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine as an off-white solid. 1H NMR (300 MHz, DMSO-d6): δ 7.45-7.32 (m, 2H), 7.21 (s, 1H), 7.13 (dd, J=9.8, 8.5 Hz, 1H), 4.59-4.21 (m, 2H), 3.47-3.25 (m, 2H), 2.88 (s, 3H), 2.25 (d, J=1.9 Hz, 3H). 19F NMR (282 MHz, DMSO-d6) δ −118.92 (m).

Aufarbeitung

  1. temperaturethe reaction mixture was cooled in ice-bath
  2. temperatureSubsequently, cooling bath
  3. customwas removed
  4. concentrationThe reaction mixture was concentrated
  5. extractionextracted with EtOAc (2×125 mL)
  6. customWorkup of the combined organic layers followed by flash column chromatographic purification (Combiflash® companion System® with RediSep® silica gel column 24 g and 30-50% EtOAc/hexanes eluting solvent)

Quellen und Nachweise

ORD-Eintrag
ord-7b526cde5753408abae04809a58862b6
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145433B2

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