Hydrochloric Acid → 4-Chloro-3,5-diethoxybenzoic acid ethyl ester

HRID 547934

Reaktionsgleichung

Reaktionsgleichung von HRID 547934
[CH2:1]([O:3][C:4](=[O:18])[C:5]1[CH:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8](N)=[C:7]([O:15][CH2:16][CH3:17])[CH:6]=1)[CH3:2].[ClH:19].N([O-])=O.[Na+].[OH-].[Na+]>O.[Cu]Cl>[CH2:1]([O:3][C:4](=[O:18])[C:5]1[CH:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([Cl:19])=[C:7]([O:15][CH2:16][CH3:17])[CH:6]=1)[CH3:2]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 123984444-Amino-3,5-diethoxybenzoic acid ethyl esterHCID 23668193Sodium Nitrite

Produkt 1

HCID 596847734-Chloro-3,5-diethoxybenzoic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 62652Cuprous chlorideKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 4-amino-3,5-diethoxy-benzoic acid ethyl ester (5.1 g, 20.13 mmol, 1.0 equiv; prepared as described in I. Kompis and A. Wick Helv. Chim. Acta 1977, 60, 3025-3034) in water (40 mL) and 37% HCl (40 mL) at 0° C. was added sodium nitrite (1.67 g, 24.16 mmol, 1.2 equiv). After 10 min, copper(I) chloride (12.0 g, 120.81 mmol, 6.0 equiv) was added, the reaction mixture stirred for an additional 5 h at 0° C. and then the ice bath removed. After stirring for 18 h, the crude reaction mixture was adjusted to pH=8 by addition of a solution of 1 M NaOH and the aqueous layer extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 5.0 g (91%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 1.32 (t, J=7.0 Hz, 4H), 1.40 (t, J=7.0 Hz, 6H), 4.09 (q, J=7.0 Hz, 4H), 4.30 (q, J=7.0 Hz, 2H), 7.18 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 13.33, 13.66, 60.29, 64.16, 105.75, 115.88, 128.25, 154.49, 165.01. MS (ISP): 273.3 [M+H]+.

Aufarbeitung

  1. customprepared
  2. customthe ice bath removed
  3. stirringAfter stirring for 18 h
  4. customthe crude reaction mixture
  5. extractionthe aqueous layer extracted with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customthe crude material purified by silica column chromatography
  9. washeluting with a gradient of heptane/ethyl acetate providing 5.0 g (91%) of the title compound

Quellen und Nachweise

ORD-Eintrag
ord-2a6966936236403c905670ff7ac6396b
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07939661B2

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