Hydrochloric Acid → Ethyl 4-(4-(2,6-difluorobenzyloxy)phenyl)-3-oxobutyrate

HRID 25015

반응식

HRID 25015 반응식
C[C:2]1([CH3:10])[O:9][C:7](=[O:8])[CH2:6][C:4](=[O:5])O1.N1C=CC=CC=1.[F:17][C:18]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:19]=1[CH2:20][O:21][C:22]1[CH:31]=[CH:30][C:25]([CH2:26]C(Cl)=O)=[CH:24][CH:23]=1.Cl>ClCCl>[F:17][C:18]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:19]=1[CH2:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([CH2:26][C:4](=[O:5])[CH2:6][C:7]([O:9][CH2:2][CH3:10])=[O:8])=[CH:30][CH:31]=1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 219645094-(2,6-Difluorobenzyloxy)benzylcarbonyl chloride

생성물 1

HCID 21964507Ethyl 4-(4-(2,6-difluorobenzyloxy)phenyl)-3-oxobutyrate

시약·촉매·용매 1

HCID 6344Dichloromethane용매3회

반응 조건

온도
0 °C

실험 절차

To a solution of Meldrum's acid (0.846 g, 5.8 mmol) in dichloromethane (5 ml) was added pyridine (2 ml) over a period of 10 minutes at 0° C. To this solution was added 4-(2,6-Difluorobenzyloxy)benzylcarbonyl chloride (Step D, 1.71 g, 5.7 mmol) in dichloromethane (5 ml), which resulted in an orange solution. The dark orange solution was stirred for 1 hour at 0° C., allowed to warm to room temperature and stirred for an additional hour. The reaction mixture was diluted with dichloromethane and poured onto 2M HCl and ice. The phases were separated and the aqueous phase was extracted twice with dichloromethane. The combined organic layers were washed twice with 2M HCl and brine, dried over Na2SO4, filtered and concentrated to a solid. The solid was suspended in abs EtOH (15 ml) and refluxed for 2.5 hours. The solvent was removed in vacuo to give a dark oil. The residue was purified by flash chromatography on silica gel column (hex:ethyl acetate, 2:1) to provide the title compound as a white solid.

후처리

  1. customresulted in an orange solution
  2. temperatureto warm to room temperature
  3. stirringstirred for an additional hour
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted twice with dichloromethane
  6. washThe combined organic layers were washed twice with 2M HCl and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a solid
  10. temperaturerefluxed for 2.5 hours
  11. customThe solvent was removed in vacuo
  12. customto give a dark oil
  13. customThe residue was purified by flash chromatography on silica gel column (hex:ethyl acetate, 2:1)

출처 및 근거

ORD 기록
ord-0e41a935a22a43f7b0ecc02577376e47
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06858602B2

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