Acetic Acid → Flurbiprofen

HRID 2285806

반응식

HRID 2285806 반응식
[F:1][C:2]1[CH:7]=[C:6]([C:8](C)([C:14]([O-])=O)[C:9]([O:11]CC)=[O:10])[CH:5]=[CH:4][C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O)(=O)C.Cl>O>[CH3:14][CH:8]([C:9]([OH:11])=[O:10])[C:6]1[CH:5]=[CH:4][C:3]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[C:2]([F:1])[CH:7]=1

참가 물질

5

반응물 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 20493003Ethyl 2-(2-fluoro-4-biphenylyl)-2-methylmalonate

생성물 1

HCID 3394Flurbiprofen수율 66.8%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

In a 200 ml round-bottom flask is placed 15.03 g (~43.7 mmol) of ethyl 2-(2-fluoro-4-biphenylyl)-2-methylmalonate, 62 ml of glacial acetic acid, and 22 ml of 6 N aqueous hydrochloric acid. The mixture is refluxed under nitrogen for 24 hours. On cooling to room temperature, the solution is diluted with 250 ml of water and the mixture is extracted with 4×50 ml of methylene chloride. The combined extracts are washed with 2×100 ml of water and then with 8×40 ml (0.2 N) of aqueous potassium hydroxide solution. Extracts 1-4 are combined, acidified to pH <1 with concentrated hydrochloric acid, and the resulting solution is extracted with 3×50 ml of methylene chloride. The organic extracts are dried over sodium sulfate and concentrated in vacuo to give 7.13 g (38.8% overall) crude flurbiprofen. Extract 5 is backwashed with 3×5 ml methylene chloride, acidified with concentrated hydrochloric acid, and the resulting mixture is extracted with 3×20 ml methylene chloride to give 1.84 g (10.0%) crude flurbiprofen. Fractions 6-8 are combined and the pH is adjusted to ~9.0. After washing with 3×30 ml methylene chloride, the aqueous is acidified with concentrated hydrochloric acid and is then extracted with 3×50 ml of methylene chloride. Drying and concentration of the extracts gives 0.53 g (4.0%) crude flurbiprofen Ib.

후처리

  1. customIn a 200 ml round-bottom flask is placed
  2. temperatureThe mixture is refluxed under nitrogen for 24 hours
  3. extractionthe mixture is extracted with 4×50 ml of methylene chloride
  4. washThe combined extracts are washed with 2×100 ml of water
  5. extractionthe resulting solution is extracted with 3×50 ml of methylene chloride
  6. dry with materialThe organic extracts are dried over sodium sulfate
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-d63112e07204412ea89cc3d7d6b1cea0
출처 데이터셋
uspto-grants-1982_04
특허 번호
US04324904

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