Isobutyl chloroformate → 6-[3-(4-Cyclohexyl-1-piperazylcarbonyl)propoxy]carbostyril

Into 200 ml of chloroform were added 5 g of 6-(3-carboxypropoxy)carbostyril and 3.2 g DBU. The outside of the reaction vessel containing the above mentioned mixture was ice-cooled and 2.8 g of isobutyl chloroformate was added dropwise to the mixture under stirring condition. After the addition operation, the reaction mixture was further stirred for 1 hour, then 3.7 g of N-cyclohexylpiperazine was added dropwise at a room temperature, and the reaction was continued for 5 hours. After the reaction was completed, the reaction mixture was washed with 1% NaOH aqueous solution and water, then dried with anhydrous sodium sulfate. The drying agent was removed by filtration and the mother liquor was concentrated. The residue thus obtained was treated by a silica-gel column chromatography (solvent used was a mixture of chloroform:methanol=30:1) to obtain elute. The elute was concentrated and the residue was recrystallized from water-containing methanol to obtain 4 g of 6-[3-(4-cyclohexyl-1-piperazylcarbonyl)propoxy]carbostyril in the form of colorless needle-like crystals. Melting point: 184.5°-186° C.

1. additionThe outside of the reaction vessel containing the
2. temperaturecooled
3. stirringAfter the addition operation, the reaction mixture was further stirred for 1 hour
4. washthe reaction mixture was washed with 1% NaOH aqueous solution and water
5. dry with materialdried with anhydrous sodium sulfate
6. customThe drying agent was removed by filtration
7. concentrationthe mother liquor was concentrated
8. customThe residue thus obtained
9. additionwas treated by a silica-gel column chromatography (solvent
10. washelute
11. concentrationThe elute was concentrated
12. customthe residue was recrystallized from water-
13. additioncontaining methanol

ORD record

ord-12658c25651341c39330c14c47f6784a

Source dataset

uspto-grants-1984_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04435404