1-Bromo-4-fluorobenzene → (1R,2R,3S)-2-(4'-fluoro-benzoyl)-3-(4-fluorophenyl)tropane

HRID 742321노트

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HRID 742321 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[Mg].[CH3:10][N:11]1[C@H:15]2[C:16]([C:19]([O:21]C)=O)=[CH:17][CH2:18][C@@H:12]1[CH2:13][CH2:14]2>C(OCC)C>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:19]([C@H:16]2[C@@H:17]([C:2]3[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=3)[CH2:18][C@H:12]3[N:11]([CH3:10])[C@@H:15]2[CH2:14][CH2:13]3)=[O:21])=[CH:3][CH:4]=1.[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:19]([C@@H:16]2[C@@H:17]([C:2]3[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=3)[CH2:18][C@H:12]3[N:11]([CH3:10])[C@@H:15]2[CH2:14][CH2:13]3)=[O:21])=[CH:3][CH:4]=1

참가 물질

6

반응물 3

HCID 99931-Bromo-4-fluorobenzeneHCID 119478(-)-Anhydroecgonine methyl esterHCID 5462224Magnesium

생성물 2

HCID 68470668(1R,2R,3S)-2-(4'-fluoro-benzoyl)-3-(4-fluorophenyl)tropaneHCID 70091550(1R,2S,3S)-2-(4'-fluoro-benzoyl)-3-(4-fluorophenyl)tropane

시약·촉매·용매 1

HCID 3283Diethyl Ether용매2회

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온도
-20 °C

실험 절차

Grignard reagent was made in a three necked reaction flask equipped with mechanical stirring, an intensive condenser and a pressure equilibrated funnel, using 4-bromo-fluorobenzene (55 ml, 500 mmol) and magnesium turnings (12.6 g, 520 mmol) in 500 ml absolute diethyl ether. The solution of grignard reagent was cooled to -20° C. and a solution of (-)-anhydroecgonine methyl ester (43 g, 233 mmol) in 200 ml absolute diethyl ether was added over 1/2 hour. The reaction was first stirred one hour at -20° C. and then 16 hours at room temperature and was finally quenched by addition of water (50 ml). The mixture was acidified by addition of hydrochloric acid (4M, 50 ml) and the aqueous phase was washed twice with diethyl ether. To the aqueous phase was added ammonium hydroxide (25%) to basic reaction and the resulting mixture was finally extracted three times with diethyl ether. After drying and concentration of the combined organic phase in vacuo. the crude product was subjected to column chromatography using diethyl ether+triethyl amine (5%) as eluent, yielding (1R,2S,3S)-2-(4'-fluoro-benzoyl)-3-(4-fluorophenyl)tropane, white crystals m.p. 178°-180° C. and (1R,2R,3S)-2-(4'-fluoro-benzoyl)-3-(4-fluorophenyl)tropane, white crystals m.p. 124°-140° C.

후처리

  1. customequipped with mechanical stirring, an intensive condenser
  2. custom16 hours at room temperature and was finally quenched by addition of water (50 ml)
  3. additionThe mixture was acidified by addition of hydrochloric acid (4M, 50 ml)
  4. washthe aqueous phase was washed twice with diethyl ether
  5. additionTo the aqueous phase was added ammonium hydroxide (25%)
  6. customto basic reaction
  7. extractionthe resulting mixture was finally extracted three times with diethyl ether
  8. customAfter drying

출처 및 근거

ORD 기록
ord-7a5baa9fca1e4300bea67c9e69835775
출처 데이터셋
uspto-grants-1996_09
특허 번호
US05554626

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