Reaktion #41856

Reaktionsgleichung

potassium carbonate

2-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chloride

(S)-6-amino-3-[(S)-2-(4′-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-7-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

sodium bicarbonate

→

(S)-7-[(S)-2-(4′-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

Ausbeute 61.7%

Lösungsmittel

water

EtOAc

EtOAc

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   WaschenThe organic layer was washed with brine
2. 2
   Trocknendried over sodium sulfate
3. 3
   Einengenconcentrated
4. 4
   workup.DISSOLUTIONThe resulting residue was dissolved in 5 mL DMF
5. 5
   workup.STIRRINGThe reaction stirred at r.t. for 3 h
6. 6
   SonstigeThe organic was dried
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe residue was purified over silica gel (-hexanes-ethyl acetate)

Vorschrift

(S)-6-amino-3-[(S)-2-(4′-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-7-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.75 mmol) was dissolved in 5 mL EtOAc, 10 mL water and 15 g sodium bicarbonate added. 2-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chloride (1.93 mmol) in 5 mL EtOAc was added to the mixture. The resulting mixture stirred at r.t. for 1.5 h. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The resulting residue was dissolved in 5 mL DMF and potassium carbonate (8.75 mmol) added. The reaction stirred at r.t. for 3 h and was poured onto ethyl acetate and water. The organic was dried and concentrated. The residue was purified over silica gel (-hexanes-ethyl acetate) to provide (S)-7-[(S)-2-(4′-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester (931 mg). LC-MS (m/z) 862.

Quelle