Reaktion #159051

Reaktionsgleichung

DIEA

5-Aza-spiro[2.4]heptane-5,6-dicarboxylic acid 5-tert-butyl ester

HATU

2-Amino-1-(4-bromo-phenyl)-ethanone bis HCl salt

→

6-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester

Ausbeute 67.0%

Lösungsmittel

DMF

ethyl acetate

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was stirred at 0° C. for 40 minutes
2. 2
   Waschenwashed with saturated sodium bicarbonate solution
3. 3
   TrocknenThe organic layer was dried (MgSO4)
4. 4
   Einengenconcentrated
5. 5
   Sonstigepurified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane)

Vorschrift

5-Aza-spiro[2.4]heptane-5,6-dicarboxylic acid 5-tert-butyl ester (350 mg, 1.45 mmol) was mixed with HATU (551 mg, 1.45 mmol) in DMF (5 mL) and the mixture was stirred at room temperature for 30 minutes. 2-Amino-1-(4-bromo-phenyl)-ethanone bis HCl salt (416 mg, 1.45 mmol) in 2 mL DMF was added, followed by DIEA (3.5 eq., 0.88 mL) dropwise at 0° C. The reaction was stirred at 0° C. for 40 minutes. The reaction mixture was diluted in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane) to give 6-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (424 mg, 67%). LCMS-ESI−: calc'd for C20H25BrN2O4: 437.33. Found: 460.1 (M+Na+).

Quelle