Sodium triacetoxyborohydride → (R)-4-(4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

HRID 1771196Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1771196
O=[CH:2][CH2:3][C@@H:4]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][C:15]=1[S:24]([C:27]([F:30])([F:29])[F:28])(=[O:26])=[O:25])[CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[Si:31]([O:38][CH2:39][CH2:40][NH:41][CH2:42][CH3:43])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH2:42][CH3:43])[CH2:2][CH2:3][C@@H:4]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][C:15]=1[S:24]([C:27]([F:29])([F:30])[F:28])(=[O:26])=[O:25])[CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]

Komponenten

5

Edukt 3

HCID 5049666Sodium triacetoxyborohydrideHCID 72666539[2-(tert-Butyldimethylsilanyloxy)ethyl]ethylamine2×HCID 86661872(R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×

Produkt 1

HCID 66723826(R)-4-(4-((2-(tert-butyldimethylsilyloxy)ethyl)(ethyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamideAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

To a solution of (R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 45, 3.98 g, 8.25 mmol) and 2-(tert-butyldimethylsilyloxy)-N-ethylethanamine (INTERMEDIATE 63, 1.68 g, 8.25 mmol) in 1,2-dichloroethane (27.5 ml) was added sodium triacetoxyborohydride (2.62 g, 12.37 mmol). The resulting mixture was stirred in the dark for 11.5 h and was then quenched with 0.5 M aqueous sodium hydroxide (50 ml). After vigorous stirring for 10 min, the opaque mixture became clear. The layers were diluted with ethyl acetate and then separated. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride before being dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (ISCO, 330 g SiO2, 50→100% ethyl acetate in hexanes for 20 mins then 0→20% methanol in ethyl acetate for 20 mins followed by 0→20% methanol in ethyl acetate over 20 min) to afford the title product (3.41 g, yield: 62%).

Aufarbeitung

  1. customwas then quenched with 0.5 M aqueous sodium hydroxide (50 ml)
  2. stirringAfter vigorous stirring for 10 min
  3. additionThe layers were diluted with ethyl acetate
  4. customseparated
  5. washThe organic layer was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  6. dry with materialbefore being dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by column chromatography (ISCO, 330 g SiO2, 50→100% ethyl acetate in hexanes for 20 mins
  10. wait0→20% methanol in ethyl acetate for 20 mins followed by 0→20% methanol in ethyl acetate over 20 min

Quellen und Nachweise

ORD-Eintrag
ord-e6fc7cef71ad4d8094e26a7ac4cfc0df
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248140B2

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