Reaktion #1927700

Reaktionsgleichung

(S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-1-[(phenylmethoxy)carbonyl]-piperidine-4-pentanoic acid

4-ethylpiperidine hydrochloride

N,N-diisopropylethylamine

→

phenylmethyl (S)-4-[4-[[(1,1-dimethylethoxy)carbonyl]amino]-5-(4-ethylpiperid-1-yl)-5-oxopentyl]piperidine-1-carboxylate

Ausbeute 95.0%

Lösungsmittel

ethyl acetate

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenis washed with 100 ml of 1N hydrochloric acid solution
2. 2
   TrocknenThe resulting product is dried over sodium sulphate
3. 3
   Filtrationis filtered
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe residue obtained
6. 6
   Sonstigeis purified by chromatography on a column of silica gel
7. 7
   Wascheneluting under pressure with a 4/6 ethyl acetate/cyclohexane mixture

Vorschrift

1.7 g (4.4 mmol) of O-(benzotriazol-1-yl)-N,N,N,N′-tetramethyluronium hexafluorophosphate (HBTU) are added portionwise, at 0° C. under nitrogen, to a solution of 1.73 g (4.0 mmol) of (S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-1-[(phenylmethoxy)carbonyl]-piperidine-4-pentanoic acid, 0.66 g (4.4 mmol) of 4-ethylpiperidine hydrochloride and 1.8 ml (10.4 mmol) of N,N-diisopropylethylamine (DIEA) in dichloromethane. The reaction mixture is allowed to warm slowly to room temperature and the reaction is continued for 18 hours. The reaction mixture is then taken up in 200 ml of ethyl acetate and is washed with 100 ml of 1N hydrochloric acid solution and then with 100 ml of saturated sodium hydrogen carbonate solution and with 100 ml of saturated sodium chloride solution. The resulting product is dried over sodium sulphate and is filtered and then concentrated. The residue obtained is purified by chromatography on a column of silica gel, eluting under pressure with a 4/6 ethyl acetate/cyclohexane mixture. 2 g of phenylmethyl (S)-4-[4-[[(1,1-dimethylethoxy)carbonyl]amino]-5-(4-ethylpiperid-1-yl)-5-oxopentyl]piperidine-1-carboxylate are obtained in the form of a viscous oil.

Quelle