Dichloromethane → Benzyl N-(tert-butoxycarbonyl)-4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-L-phenylalaninate

HRID 724704ノート

反応式

HRID 724704 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:20][C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1)[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:36]([N:40]1[C:44](=[O:45])[CH:43]=[C:42](Cl)[S:41]1(=[O:48])=[O:47])([CH3:39])([CH3:38])[CH3:37].ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:10]([O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:11])[CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:42]2[S:41](=[O:47])(=[O:48])[N:40]([C:36]([CH3:38])([CH3:37])[CH3:39])[C:44](=[O:45])[CH:43]=2)=[CH:25][CH:26]=1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 218786382-Tert-butyl-5-chloro-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trioneHCID 58746674benzyl(2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate

生成物 1

HCID 11720867Benzyl N-(tert-butoxycarbonyl)-4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-L-phenylalaninate収率 37.3%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A solution of benzyl(2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate (3.33 g, 6.92 mmol), 2-tert-Butyl-5-chloro-1,1-dioxo-1,2-dihydro-1λ6-isothiazol-3-one (1.86 g, 8.31 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.68 g, 0.83 mmol), and potassium carbonate (4.78 g, 0.0346 mol) in 1,4-dioxane (25 mL) were added to a flask with a reflux condenser. The reaction atmosphere was evacuated and purged four times with dry nitrogen. The reaction was heated at 80° C. overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. ethyl acetate extracts were washed with saturated brine and dried over anhyd. sodium sulfate, filtered and concentrated to an oil. The crude was eluted with 10%–30% ethyl acetate in hexanes to give the product (1.4 g, 37%). LCMS found for C28H35N2O7S (M+H)+: m/z=543.

後処理

  1. customThe reaction atmosphere
  2. customwas evacuated
  3. custompurged four times with dry nitrogen
  4. additionThe reaction mixture was diluted with water
  5. extractionextracted with ethyl acetate
  6. washethyl acetate extracts were washed with saturated brine
  7. customdried over anhyd
  8. filtrationsodium sulfate, filtered
  9. concentrationconcentrated to an oil
  10. washThe crude was eluted with 10%–30% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-6c28f0cff75747ce972d1b25bbb695a8
出典データセット
uspto-grants-2006_11
特許番号
US07141596B2

反応ノート

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