Hydrochloric Acid → 9-Chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid ethyl ester

HRID 411847

Reaktionsgleichung

Reaktionsgleichung von HRID 411847
[NH2:1][C:2]1[C:3]([C:12](=O)[CH2:13][Cl:14])=[CH:4][C:5]2[O:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.C(N([CH2:21][CH3:22])CC)C.C([CH:25]([C:29](Cl)=[O:30])[C:26](Cl)=[O:27])C.Cl.[OH2:33]>C(#N)C>[CH2:21]([O:33][C:29]([C:25]1[C:26](=[O:27])[NH:1][C:2]2[CH:11]=[C:6]3[O:7][CH2:8][CH2:9][O:10][C:5]3=[CH:4][C:3]=2[C:12]=1[CH2:13][Cl:14])=[O:30])[CH3:22]

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 8471Triethylamine2×HCID 102428551-(7-Amino-2,3-dihydro-1,4-benzodioxin-6-yl)-2-chloroethan-1-oneHCID 109209242-Ethylpropanedioyl dichloride

Produkt 1

HCID 110672879-Chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid ethyl esterAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a mixture of 1-(7-amino-2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-chloro-ethanone (230 g. 1.01 mol) prepared as described in Intermediate 12, in acetonitrile (1.5 L) and triethylamine (197 mL, 1.41 mol, 1.4 eq) is added ethyl malonyl chloride (180 mL, 1.41 mol, 1.4 eq) over 0.5 h while keeping the reaction temperature less than 30° C. with an ice bath. After the addition is complete the reaction is stirred 1.5 h at room temperature. A second charge of Triethylamine (140 mL, 1.01 mol, 1.0 eq) is added and the reaction is stirred for 4.5 hours. Water (2.1 L) is added slowly followed by conc. HCl (115 mL). The slurry is stirred overnight at rt, filtered, and the solid washed with water (460 mL). The solid is then dried under high vacuum (about 1 mm Hg) at 40° C. to give 270 g (83%) 9-chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid ethyl ester as a yellow solid. HRMS (EI+): calc for C15H14NO5Cl: 323.0561, Found: 323.0556.

Aufarbeitung

  1. customprepared
  2. customthe reaction temperature less than 30° C.
  3. additionAfter the addition
  4. additionis added
  5. stirringthe reaction is stirred for 4.5 hours
  6. stirringThe slurry is stirred overnight at rt
  7. filtrationfiltered
  8. washthe solid washed with water (460 mL)
  9. customThe solid is then dried under high vacuum (about 1 mm Hg) at 40° C.

Quellen und Nachweise

ORD-Eintrag
ord-fd46dc862bf9473d8dd7dade3870ea4e
Quelldatensatz
uspto-grants-2003_05
Patentnummer
US06559309B2

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