Triethylamine → 4-Methyl-4-p-nitrobenzyloxycarbonylaminovaleric acid p-methoxybenzyl ester

Temperatur

0 °C

To a mixture of 4-carboxy-4-methylvaleric acid p-methoxybenzyl ester (35.43 g) and triethylamine (14.14 g) in dry tetrahydrofuran (167 ml) was added dropwise a solution of ethyl chloroformate (15.23 g) in dry tetrahydrofuran (50 ml) with ice-cooling, and the mixture was stirred at 0° C. for 15 minutes. The precipitate was removed by filtration, and the filtrate was added dropwise to sodium azide (7.4 g) in water (67 ml) at a temperature up to 0° C. with stirring, followed by stirring for 30 minutes at the same temperature. The reaction mixture was diluted with benzene (200 ml) and the aqueous layer was extracted with benzene (100 ml). The combined benzene solution was washed with water, dried over anhydrous sodium sulfate and allowed to stand overnight at room temperature. After concentration to a volume of 100 to 120 ml in vacuo at a temperature below 30° C., the solution was stirred for 1 hour at 80° to 90° C. and evaporated to give an oily residue. p-Nitrobenzyl alcohol (23.32 g) and dry dioxane (22 ml) was added to the residue and the mixture was stirred for 7 hours at 120° to 130° C. and evaporated in vacuo to give an oily residue which was then purified by silica gel chromatography to give 4-methyl-4-p-nitrobenzyloxycarbonylaminovaleric acid p-methoxybenzyl ester.

1. temperaturecooling
2. customThe precipitate was removed by filtration
3. additionthe filtrate was added dropwise to sodium azide (7.4 g) in water (67 ml) at a temperature up to 0° C.
4. stirringwith stirring
5. stirringby stirring for 30 minutes at the same temperature
6. additionThe reaction mixture was diluted with benzene (200 ml)
7. extractionthe aqueous layer was extracted with benzene (100 ml)
8. washThe combined benzene solution was washed with water
9. dry with materialdried over anhydrous sodium sulfate
10. waitto stand overnight at room temperature
11. concentrationAfter concentration to a volume of 100 to 120 ml in vacuo at a temperature below 30° C.
12. stirringthe solution was stirred for 1 hour at 80° to 90° C.
13. customevaporated
14. customto give an oily residue
15. stirringthe mixture was stirred for 7 hours at 120° to 130° C.
16. customevaporated in vacuo
17. customto give an oily residue which
18. customwas then purified by silica gel chromatography

ORD-Eintrag

ord-3a5368946166437abb93c7cc7c75127f

Quelldatensatz

uspto-grants-1988_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04742052