Reaktion #748391

Reaktionsgleichung

carboxylic acid

5-(4-Ethylphenyl)-1-[(4-hydroxypiperidin-1-yl)carbonyl]piperidine-3-carboxylic acid

PYBOP

N,N′-diisopropylethylamine

hydroxyguanidine hemisulphate hemihydrate

N,N′-diisopropylethylamine

→

[3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-(4-ethylphenyl)piperidin-1-yl](4-hydroxypiperidin-1-yl)methanone

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction mixture was stirred at RT for 1 h
2. 2
   Filtrationfiltered through a frit
3. 3
   WaschenThe residue was washed with 50 ml of DMF
4. 4
   workup.STIRRINGthe combined organic phases were stirred at 130° C. (preheated oil bath) for 40 min
5. 5
   SonstigeSubsequently, the solvent was removed under reduced pressure
6. 6
   workup.STIRRINGstirred vigorously for 24 h
7. 7
   SonstigeThe organic phase was removed
8. 8
   Extraktionthe aqueous phase was extracted with dichloromethane
9. 9
   TrocknenThe organic phase was dried over magnesium sulphate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated under reduced pressure

Vorschrift

Under argon, a solution of 2.50 g (6.31 mmol) of the carboxylic acid from Example 21A in 50 ml of DMF was admixed at RT with 3.94 g (7.57 mmol) of PYBOP and 2.20 ml (12.6 mmol) of N,N′-diisopropylethylamine. Subsequently, the mixture was stirred at RT for 30 min and then the solution was added dropwise within 1.5 h to a suspension of 5.04 g (18.9 mmol) of hydroxyguanidine hemisulphate hemihydrate, 3.30 ml (18.9 mmol) of N,N′-diisopropylethylamine and 4 Å molecular sieve. The reaction mixture was stirred at RT for 1 h and then filtered through a frit. The residue was washed with 50 ml of DMF and then the combined organic phases were stirred at 130° C. (preheated oil bath) for 40 min. Subsequently, the solvent was removed under reduced pressure and the residue was admixed with 30 ml of diethyl ether and 30 ml of 1 N aqueous sodium hydroxide solution, and stirred vigorously for 24 h. The organic phase was removed and the aqueous phase was extracted with dichloromethane. The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. Yield: 3.00 g (77% of theory, purity 65%)

Quelle