Tetrahydrofuran → Vanillin

Temperatur

-10 °C

To a 250 ml. three-necked flask fitted with a stopper, thermometer, drying tube and magnetic stirring bar was added 4.28 g. (0.010 mole) of beta-benzyl-N-benzyloxycarbonyl-L-aspartyl-D-alanine, 75 ml. tetrahydrofuran and 1.53 ml. (0.011 mole) triethylamine. The mixture was cooled to -10° C., 1.05 ml. (0.011 mole) ethyl chloroformate was added, stirred for 20 minutes, cooled to -35° C. and 1.11 g. (0.010 mole) of dicyclopropylcarbinylamine added. The reaction mixture was allowed to warm slowly to room temperature and stirred overnight. The mixture was poured into 150 ml. water, extracted with 250 ml. of ethyl acetate and the organic phase washed with 5% aqueous sodium bicarbonate (2×75 ml.), 3 M hydrochloric acid (2×75 ml.), brine (1×100 ml.) and dried over anhydrous magnesium sulfate. The dried extract was evaporated to dryness in vacuo to provide a colorless solid which was recrystallized from 75 ml. of boiling ethyl acetate to obtain 3.78 g. (72%) of diblocked amide, M.P. 164°-165° C. Thin-layer chromatography (TLC) on silica gel, eluting with 1:1 ethyl acetate/hexane gave a single spot, Rf 0.40 with vanillin spray reagent. An additional 0.65 g. was recovered from the mother liquors.

1. customthree-necked flask fitted with a stopper
2. customthermometer, drying tube and magnetic stirring bar
3. additionwas added 4.28 g
4. temperaturecooled to -35° C.
5. addition(0.010 mole) of dicyclopropylcarbinylamine added
6. temperatureto warm slowly to room temperature
7. stirringstirred overnight
8. additionThe mixture was poured into 150 ml
9. extractionwater, extracted with 250 ml
10. washof ethyl acetate and the organic phase washed with 5% aqueous sodium bicarbonate (2×75 ml.), 3 M hydrochloric acid (2×75 ml.), brine (1×100 ml.)
11. dry with materialdried over anhydrous magnesium sulfate
12. extractionThe dried extract
13. customwas evaporated to dryness in vacuo
14. customto provide a colorless solid which
15. customwas recrystallized from 75 ml
16. customof boiling ethyl acetate to obtain 3.78 g
17. washThin-layer chromatography (TLC) on silica gel, eluting with 1:1 ethyl acetate/hexane

ORD-Eintrag

ord-29c58e78ad78480f941a5cb7cd0149d3

Quelldatensatz

uspto-grants-1989_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04804782