Chlorotrimethylsilane → 3-chloro-2-methoxy-6-[(1E)-3-[4-(methylsulfonyl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)prop-1-en-2-yl]pyridine

HRID 70612

반응식

HRID 70612 반응식
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:5][CH:4]=1.C[Si](Cl)(C)C.BrCCBr.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.Br/[C:39](/[C:47]1[N:52]=[C:51]([O:53][CH3:54])[C:50]([Cl:55])=[CH:49][CH:48]=1)=[CH:40]\[CH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>O1CCCC1.[Zn].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>[Cl:55][C:50]1[C:51]([O:53][CH3:54])=[N:52][C:47](/[C:39](/[CH2:2][C:3]2[CH:8]=[CH:7][C:6]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:5][CH:4]=2)=[CH:40]/[CH:41]2[CH2:42][CH2:43][O:44][CH2:45][CH2:46]2)=[CH:48][CH:49]=1

참가 물질

10

반응물 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 521585Tris(furan-2-yl)phosphaneHCID 27335814-(Methylsulfonyl)benzyl BromideHCID 584525136-[(Z)-1-bromo-2-(tetrahydro-2H-pyran-4-yl)ethenyl]-3-chloro-2-methoxypyridine

생성물 1

HCID 673980903-chloro-2-methoxy-6-[(1E)-3-[4-(methylsulfonyl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)prop-1-en-2-yl]pyridine수율 59%

시약·촉매·용매 4

HCID 23994Zinc촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
80 °C

실험 절차

1-(Bromomethyl)-4-(methylsulfonyl)benzene (110 mg), trimethylsilyl chloride (12.5 μL) and 1,2-dibromoethane (8.6 μL) were added to a solution of zinc powder (78 mg) in tetrahydrofuran (4 mL) in the presence of an argon gas, and the mixture was stirred at 80° C. for two hours. The reaction solution was returned to room temperature. A solution of tris(dibenzylideneacetone)dipalladium (45 mg), tri(2-furyl)phosphine (69 mg) and 6-[(Z)-1-bromo-2-(tetrahydro-2H-pyran-4-yl)ethenyl]-3-chloro-2-methoxypyridine (380 mg) in tetrahydrofuran (2 mL) was added and the mixture was stirred at 90° C. for two hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1) to give 3-chloro-2-methoxy-6-[(1E)-3-[4-(methylsulfonyl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)prop-1-en-2-yl]pyridine as a yellow oil (110 mg).

후처리

  1. customwas returned to room temperature
  2. stirringthe mixture was stirred at 90° C. for two hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was then evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1→0:1)

출처 및 근거

ORD 기록
ord-8416f17639ed4d268133cfb7d52e8403
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822503B2

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