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

HRID 547934

반응식

HRID 547934 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 62652Cuprous chloride촉매HCID 962Water용매

반응 조건

온도
0 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-2a6966936236403c905670ff7ac6396b
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07939661B2

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