Propanal → methyl (S)-N-tert-butoxycarbonyl-4-(1-hydroxy-1-propyl)pyroglutamate

Temperature

-78 °C

To 40 ml of tetrahydrofuran were added 1.5 ml of diisopropylamine and 6.9 ml of 1.6M butyllithium-hexane solution at -78° C. in a stream of nitrogen, followed by stirring for 10 minutes. A solution of 2.43 g of methyl (S)-N-tert-butoxycarbonylpyroglutamate in 15 ml of tetrahydrofuran was added to the reaction mixture and the resulting mixture was stirred for 10 minutes at -78° C. and then for 20 minutes at -40° C. To the reaction mixture which was again cooled to -78° C. and then was added dropwise a solution of 0.8 ml of propionaldehyde in 4 ml of tetrahydrofuran. After stirring for 10 minutes, the reaction mixture was added with a saturated ammonium chloride aqueous solution and stirred until the temperature of the mixture reached room temperature. The reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with water and a saturated saline solution, dried over sodium sulfate and distilled to remove the solvent. The residue was subjected to a column (2.5×40 cm) chromatography (developed by ethyl acetate-hexane×1:3→1:2→1:1) to obtain 1.2 g (40%) of methyl (S)-N-tert-butoxycarbonyl-4-(1-hydroxy-1-propyl)pyroglutamate as colorless oil.

1. stirringthe resulting mixture was stirred for 10 minutes at -78° C.
2. waitfor 20 minutes at -40° C
3. stirringAfter stirring for 10 minutes
4. stirringstirred until the temperature of the mixture
5. customreached room temperature
6. extractionThe reaction mixture was extracted with ethyl acetate
7. washThe combined organic layers were washed with water
8. dry with materiala saturated saline solution, dried over sodium sulfate
9. distillationdistilled
10. customto remove the solvent

ORD record

ord-ebd647101a814db7b491bdeec7ea7c3b

Source dataset

uspto-grants-1991_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05021439