Citric Acid → (e)-2-[2-(Tert-butoxy)-2-oxoethyl]-5-cyclohexyl-2-pentenoic acid cyclohexylamine salt

Temperatur

0 °C

Potassium tert-butoxide (20.2 g, 0.18 mol) was added portionwise over 10 minutes to a solution of 3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester (25.4 g, 82- mmol) in THF (115 ml), at 0° C., under nitrogen. The mixture was stirred at 0° C. for 40 minutes and then cooled to −20° C. A solution of 3-cyclohexylpropan-1 -al (11.5 g, 82 mmol in THF (60 ml) was added dropwise over 10 minutes between −20 and −10° C., under nitrogen. The mixture was stirred between −20 and −5° C. for 3 hours and then aqueous citric acid (10%, 250 ml) and ethyl acetate (200 ml) was added. The organic phase was separated and the aqueous fraction was washed with ethyl acetate (200 ml). The combined organic fractions were washed with saturated sodium bicarbonate solution (2×100 ml), aqueous citric acid solution (10%, 100 ml) and demineralised water (100 ml) and then concentrated in vacuo. The resulting solid was taken up in ethyl acetate (150 ml) and cyclohexylamine (9.4 ml, 82 mmol) was added dropwise over 5 minutes at 20-25° C. The mixture was stirred at 20-25° C. for 16 hours and then filtered. The residue was dried in vacuo at 40° C. for 4 hours to leave the title compound as a colourless solid (21.7 g, 67% yield, 95% pure by NMR).

1. temperaturecooled to −20° C
2. stirringThe mixture was stirred between −20 and −5° C. for 3 hours
3. customThe organic phase was separated
4. washthe aqueous fraction was washed with ethyl acetate (200 ml)
5. washThe combined organic fractions were washed with saturated sodium bicarbonate solution (2×100 ml), aqueous citric acid solution (10%, 100 ml) and demineralised water (100 ml)
6. concentrationconcentrated in vacuo
7. stirringThe mixture was stirred at 20-25° C. for 16 hours
8. filtrationfiltered
9. customThe residue was dried in vacuo at 40° C. for 4 hours

ORD-Eintrag

ord-f4665266944c4ae1bbd06e1ce8d7228d

Quelldatensatz

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06452041B1