Reaktion #1815189

Reaktionsgleichung

N,N′-diisopropylethylamine

racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-fluoro-2-methylphenyl)-2,3-dihydro-1′-[(tert-butoxycarbonyl)methyl]-2,6′-dioxospiro[indole-3,3′-piperidine] 1-methoxyethyl trimethylsilane

trifluoroacetic acid

→

racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-fluoro-2-methylphenyl)-1′-hydroxycarbonylmethylspiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione

Ausbeute 75.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction mixture was concentrated
2. 2
   workup.DISSOLUTIONThe residue was redissolved in methanol (10 mL)
3. 3
   Temperaturthe crude was refluxed for 1 h
4. 4
   EinengenThe reaction mixture was concentrated
5. 5
   Sonstigethe residue was partitioned between ethyl acetate and HCl aqueous solution (1N)
6. 6
   SonstigeThe organic layer was separated
7. 7
   Trocknendried over MgSO4
8. 8
   Einengenconcentrated
9. 9
   SonstigeThe residue was triturated with ethyl acetate and hexane

Vorschrift

To a solution of racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-fluoro-2-methylphenyl)-2,3-dihydro-1′-[(tert-butoxycarbonyl)methyl]-2,6′-dioxospiro[indole-3,3′-piperidine]-1-methoxyethyl trimethylsilane (0.54 g, 0.76 mmol) prepared in example 55c in dichloromethane (10 mL) was added trifluoroacetic acid (20 mL). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated. The residue was redissolved in methanol (10 mL). To the resulting solution was added N,N′-diisopropylethylamine (1 mL, 5.53 mmol) and the crude was refluxed for 1 h. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and HCl aqueous solution (1N). The organic layer was separated, dried over MgSO4 and concentrated. The residue was triturated with ethyl acetate and hexane to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-fluoro-2-methylphenyl)-1′-hydroxycarbonylmethylspiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 0.3 g, 75%).

Quelle