Sodium Hydroxide → (R)-di-tert-butyl 2-(ethyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphate

HRID 1771185Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1771185
[P:1]([O:13][CH2:14][CH2:15][NH:16][CH2:17][CH3:18])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].O=[CH:20][CH2:21][C@@H:22]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([S:38]([NH2:41])(=[O:40])=[O:39])=[CH:34][C:33]=1[S:42]([C:45]([F:48])([F:47])[F:46])(=[O:44])=[O:43])[CH2:23][S:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.C(Cl)Cl>[P:1]([O:13][CH2:14][CH2:15][N:16]([CH2:17][CH3:18])[CH2:20][CH2:21][C@@H:22]([NH:31][C:32]1[CH:37]=[CH:36][C:35]([S:38](=[O:39])(=[O:40])[NH2:41])=[CH:34][C:33]=1[S:42]([C:45]([F:48])([F:46])[F:47])(=[O:43])=[O:44])[CH2:23][S:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:2]

Komponenten

7

Edukt 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 58080210Di-tert-butyl 2-(ethylamino)ethyl phosphate2×HCID 86661872(R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide2×

Produkt 1

HCID 66723800(R)-di-tert-butyl 2-(ethyl(4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butyl)amino)ethyl phosphateAusbeute 50,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of di-tert-butyl 2-(ethylamino)ethyl phosphate (INTERMEDIATE 49, 455 mg, 1.62 mmol) in 1,2-dichloroethane (0.5 ml) at r.t was added to a solution (R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 45, 0.78 g, 1.62 mmol) and 1,2-dichloroethane (10.0 ml). The resulting reaction mixture was stirred for 15 minutes at r.t and solid sodium triacetoxyborohydride (0.514 g, 2.42 mmol) was added. The resulting mixture was stirred at r.t for 4 hours. A solution of NaOH (aq., 0.5 N, 40 ml) and DCM (20 ml) were added to the reaction mixture. After stirring for 15 min at r.t, the layers were separated. After separation, the organic layer was washed with saturated NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo. The concentrate was purified by column chromatography (ISCO, silica gel, eluting with 0→100% EtOAc/hexanes) to give the title compound (610 mg, yield: 50%).

Aufarbeitung

  1. customThe resulting reaction mixture
  2. additionwas added
  3. stirringAfter stirring for 15 min at r.t
  4. customthe layers were separated
  5. customAfter separation
  6. washthe organic layer was washed with saturated NaHCO3, brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe concentrate was purified by column chromatography (ISCO, silica gel, eluting with 0→100% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a00a971cfc414baeb557210f3e7fa870
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248140B2

Notizen zur Reaktion

Wird geladen…