Hydrochloric Acid → 3-Pyridinecarboxylic acid, 2-(2,4-dichlorophenoxy)-

HRID 1877363노트

반응식

HRID 1877363 반응식
Cl[C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Cl:11][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[OH:19].C(=O)([O-])[O-].[Cs+].[Cs+].Cl>C1(C)C=CC=CC=1.O.CC#N.CC#N.CC#N.CC#N.F[P-](F)(F)(F)(F)F.[Cu+]>[Cl:11][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[O:19][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 84492,4-DichlorophenolHCID 10796Cesium carbonateHCID 762582-Chloronicotinic acid

생성물 1

HCID 2158923-Pyridinecarboxylic acid, 2-(2,4-dichlorophenoxy)-

시약·촉매·용매 3

HCID 11068737tetrakis(acetonitrile)copper(I) hexafluorophosphate촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

To a solution of 2-chloro-nicotinic acid (2.15 g, 13.65 mmol, 1.0 equiv; [CAS RN 2942-59-8]) and 2,4-dichloro-phenol (2.22 g, 13.65 mmol, 1.0 equiv; [CAS RN 120-83-2]) in toluene (40 mL) was added caesium carbonate (8.89 g, 27.29 mmol, 2.0 equiv; [CAS RN 534-17-8]) and tetrakis(acetonitrile)copper(I) hexafluorophosphate (1.02 g, 2.73 mmol, 0.2 equiv; [CAS RN 64443-05-6]). The reaction mixture was heated to reflux over night. The solvent was evaporated under reduced pressure and the crude reaction product taken up in water (100 mL) acidified to pH 1 by addition of a solution of 1 M HCl and extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of dichloromethane/methanol affording 1.69 g (44%) of the title compound as an off-white solid. 1H NMR (400 MHz, DMSO): δ7.26 (dd, J=7.6 Hz, J=4.8 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 7.49 (dd, J=8.7 Hz, J=2.6 Hz, 1H), 7.76 (d, J=2.4 Hz, 1H), 8.25 (dd, J=4.8 Hz, J=2.2 Hz, 1H), 8.30 (dd, J=7.5 Hz, J=2.2 Hz, 1H), 13.33 (s, 1H). MS (ISN): 282.3 [M−H]−.

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux over night
  3. customThe solvent was evaporated under reduced pressure
  4. customthe crude reaction product
  5. extractionextracted with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organic phases were dried over MgSO4
  7. customthe product purified by silica column chromatography
  8. washeluting with a gradient of dichloromethane/methanol affording 1.69 g (44%) of the title compound as an off-white solid

출처 및 근거

ORD 기록
ord-d5b1c8c62093478d956402d0bc540093
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309734B2

반응 노트

불러오는 중…