Tetrahydrofuran → Vanillin

温度

-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.), 3M 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. C. To a slurry of 2.58 g. (4.9 mmole) of the product obtained in Part B in 250 ml. of methanol was added 0.60 g. of 5% palladium-on-carbon catalyst (50% wet) and the mixture hydrogenated for one hour at an initial pressure of 71 psi (5.0 kg./cm.2). The catalyst was removed by filtration and the methanol evaporated at reduced pressure to afford 1.47 g. (100%) of colorless product, M.P. 190°-191° C. TLC in 4:1:1 butanol/water/acetic acid (v/v) and spraying with ninhydrin gave a single spot, Rf 0.36.

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.), 3M 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レコード

ord-74dbfcb04100416f8698a15d3e1b046f

出典データセット

uspto-grants-1989_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04855454