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

HRID 724704노트

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HRID 724704 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

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

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온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6c28f0cff75747ce972d1b25bbb695a8
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07141596B2

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