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Sodium Carbonate → 1-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-5-vinyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one

HRID 1854573
ノート
印刷プレビュー

反応式

HRID 1854573 の反応式
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[N:6]([C:13](=[O:23])[CH2:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:22])[C@H:7]2[CH3:12].[CH2:33](OB(C=C)OCCCC)[CH2:34]CC.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Si:26]([O:25][CH2:24][C@H:5]1[CH2:4][C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[CH:33]=[CH2:34])[C@H:7]([CH3:12])[N:6]1[C:13](=[O:23])[CH2:14][C:15]1[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:22])([C:29]([CH3:30])([CH3:32])[CH3:31])([CH3:28])[CH3:27]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 236543Dibutyl Vinylboronate (stabilized with Phenothiazine)HCID 1238139441-((1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one

生成物 1

HCID 1235332471-((1S,3R)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-5-vinyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one収率 94.6%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

Dissolve 1-((1S,3R)-5-bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-chloro-6-fluorophenyl)ethan-1-one (1.8 g, 3.33 mmol) and vinylboronic acid dibutyl ester (1.5 mL, 6.65 mmol) in 1,4-dioxane (22 mL). Add aqueous Na2CO3 solution (11 mL, 2M in water). Degas with nitrogen 10 min Add bis(triphenylphosphine)palladium(II) chloride (467 mg, 0.67 mmol). Heat to 80° C. Stir 2 hours. Add water and extract with ethyl acetate three times. Combine the ethyl acetate extracts, dry over sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with ethyl acetate: hexanes (gradient, 5-40%) to give the title compound as a white foam (1.54 g, 3.15 mmol). MS (m/z): 488.2 (M+1).

後処理

  1. customDegas with nitrogen 10 min
  2. extractionAdd water and extract with ethyl acetate three times
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customto give a residue
  7. customPurify the residue by silica gel chromatography
  8. washeluting with ethyl acetate

出典と根拠

ORDレコード
ord-37f2220a0295496f911e9c4ca1a80530
出典データセット
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08962654B2

反応ノート

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