1-Bromo-3,5-bis(trifluoromethyl)benzene → (3S)-1-[3,5-bis(trifluoromethyl)phenyl]pyrrolidin-3-ol

HRID 2198027노트

반응식

HRID 2198027 반응식
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.[OH:17][C@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([N:20]2[CH2:21][CH2:22][C@H:18]([OH:17])[CH2:19]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

참가 물질

8

반응물 4

HCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 634876Binap, (A+-)-HCID 22309122(S)-3-Hydroxypyrrolidine hydrochlorideHCID 23676156Sodium t-butoxide

생성물 1

HCID 46941682(3S)-1-[3,5-bis(trifluoromethyl)phenyl]pyrrolidin-3-ol수율 28%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

A solution of 3,5-bis(trifluoromethyl)phenyl bromide (44.0 g), (S)-3-hydroxypyrrolidine hydrochloride (17.8 g), tris(dibenzylideneacetone)dipalladium(0) (5.88 g), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (8.00 g) and sodium tert-butoxide (36.0 g) in toluene (280 ml) was refluxed with stirring under an argon gas atmosphere for 16 hr. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate 20:1-2:1) to give the title compound (12.0 g, yield 28%) as a white solid.

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate 20:1-2:1)

출처 및 근거

ORD 기록
ord-e645636b00b045c4adfdb98b6337d8c4
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08338622B2

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