Reaktion #159121

Reaktionsgleichung

HCl

DIPEA

2-Amino-1-(4-bromo-phenyl)-ethanone hydrochloride

HATU

LiOH

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

→

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

Ausbeute 100.0%

Lösungsmittel

DMF

EtOAc

MeOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionthe aqueous phase was extracted 3× with DCM
2. 2
   TrocknenThe combined organics were dried over MgSO4
3. 3
   Filtrationfiltered
4. 4
   Einengenconcentrated
5. 5
   workup.ADDITIONwas added dropwise
6. 6
   workup.ADDITIONImmediately after addition
7. 7
   Temperaturthe reaction mixture was warmed to room temperature
8. 8
   WaschenThe organic layer was washed with saturated aqueous NaHCO3 and brine
9. 9
   Trocknendried over MgSO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    SonstigeThe crude residue was purified by silica column chromatography (30% to 50% EtOAc/hexane)

Vorschrift

5-Aza-spiro[2.4]heptane-5,6-dicarboxylic acid 5-benzyl ester (361 mg, 1.25 mmol) was dissolved in MeOH (10 mL) and LiOH (1 M in H2O, 5 mL, 5 mmol) was added. After stirring for 15 hours at room temperature, the reaction mixture was poured into 10% HCl and the aqueous phase was extracted 3× with DCM. The combined organics were dried over MgSO4, filtered and concentrated. The residue was treated with 2-Amino-1-(4-bromo-phenyl)-ethanone hydrochloride (344 mg, 1.38 mmol), HATU (525 mg, 1.38 mmol) and DMF (14 mL). The suspension was stirred at 0° C. for 21 minutes before DIPEA (0.72 mL, 4.1 mmol) was added dropwise. Immediately after addition, the reaction mixture was warmed to room temperature. 40 minutes later the mixture was diluted with EtOAc. The organic layer was washed with saturated aqueous NaHCO3 and brine, then dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (30% to 50% EtOAc/hexane) to afford 6-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester (589 mg, 100%).

Quelle