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

反応式

HRID 70612 の反応式
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

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-8416f17639ed4d268133cfb7d52e8403
出典データセット
uspto-grants-2014_09
特許番号
US08822503B2

関連ノート

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