Citric Acid → Ethyl 7-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1H-indole-2-carboxylate

HRID 925636

Reaktionsgleichung

Reaktionsgleichung von HRID 925636
[H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([F:18])[CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9]2.[C:19]([O:23][C:24]([N:26]1[CH2:30][CH2:29]OS1(=O)=O)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH2:16]([O:15][C:13]([C:10]1[N:11]([CH2:29][CH2:30][NH:26][C:24]([O:23][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:25])[C:12]2[C:8]([CH:9]=1)=[CH:7][C:6]([F:18])=[CH:5][C:4]=2[Br:3])=[O:14])[CH3:17]

Komponenten

6

Edukt 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 21014457Ethyl 7-bromo-5-fluoro-1H-indole-2-carboxylateHCID 235840203-Boc-1,2,3-oxathiazolidine 2,2-dioxide

Produkt 1

HCID 90036188Ethyl 7-bromo-1-(2-((tert-butoxycarbonyl)amino)ethyl)-5-fluoro-1H-indole-2-carboxylateAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a stirred mixture of sodium hydride [disp. 55-65%] (175 mg, 4.37 mmol) in DMF (5.6 ml) was added drop wise at room temperature under argon atmosphere a solution of commercially available ethyl 7-bromo-5-fluoro-1H-indole-2-carboxylate [CAS No. 396076-60-1] (1.04 g, 3.64 mmol) in DMF (2.8 ml). Afterwards the mixture was allowed to stir for 5 min at room temperature, then commercially available 2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester [CAS No. 459817-82-4] (975 mg, 4.37 mmol) was added and the solution was allowed to stir at room temperature for 15 h. The solution was cooled in an ice bath, and citric acid (10%, 62 ml) was added drop wise. The mixture was allowed to stir at room temperature for 1 h, and was afterwards extracted with ethyl acetate (2×70 ml). The combined organic layers were washed with brine (80 ml), dried (MgSO4) and evaporated. The crude material (2.04 g) was purified by flash chromatography on silica gel (heptan/ethyl acetate 0-80%) to yield 7-bromo-1-(2-tert-butoxycarbonylamino-ethyl)-5-fluoro-1H-indole-2-carboxylic acid ethyl ester as a light yellow oil (1.37 g, 88%), MS (ISN) m/z=431.2 [(M+H)+].

Aufarbeitung

  1. addition459817-82-4] (975 mg, 4.37 mmol) was added
  2. stirringto stir at room temperature for 15 h
  3. temperatureThe solution was cooled in an ice bath
  4. stirringto stir at room temperature for 1 h
  5. extractionwas afterwards extracted with ethyl acetate (2×70 ml)
  6. washThe combined organic layers were washed with brine (80 ml)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe crude material (2.04 g) was purified by flash chromatography on silica gel (heptan/ethyl acetate 0-80%)

Quellen und Nachweise

ORD-Eintrag
ord-0908f6b63e594a4bbc9b84e72f43b7bb
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284321B2

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