| Synthesis |
Kev npaj ntawm trans {{0}}amino-cyclohexyl-acetic acid ethyl ester HClA 2500 1 enamelled autoclave yog them nrog 100}0 kg ntawm deionized dej thiab 210 kg (1.16 kM) ntawm 4-nitrophenyl-acetic acid ntawm chav tsev kub hauv qab cua nitrogen. Tom qab inertisation los ntawm nitrogen rau qhov sib tov tau txais kev ncua ntawm 21 kg ntawm 10% Pd / C hauv 20 kg ntawm deionized dej yog ntxiv thiab cov catalyst ntsuas ntsuas yog rinsed los ntawm ntxiv 20 kg ntawm deionized dej. Tom qab yaug cov tshuaj tiv thaiv cov hlab ntsha los ntawm hydrogen gas, hydrogenation yog nqa tawm ntawm qhov kub thiab txias ntawm 44-46??C thiab qis dua mus txog 0,6 bar overpressure kom txog thaum hydrogen uptake qeeb. Tom qab txo cov nitro pab pawg qhov kub thiab txias tau coj mus rau 55- 58??C thiab hydrogenation txuas ntxiv tuav hydrogen siab ntawm max. 4.0 bar overpressures. Tom qab ua tiav ntawm hydrogen uptake, qhov sib tov yog txias rau qhov kub ntawm 25-30??C, purged nrog nitrogen thiab cov catalyst yog lim rau ntawm Spakler lim nyob rau hauv pressurized nitrogen. Cov tshuaj tiv thaiv hlab ntsha, lim thiab cov kab yog ntxuav ntxiv 200 g ntawm deionized dej. Cov filtrates tau ua ke thiab nyob rau hauv ib qho 2500 1 enamelled doubler 1200 kg ntawm distillate yog distilled ntawm txog 80??C sab hauv kub hauv lub tshuab nqus tsev. Cov residue tau txais yog txias rau qhov kub qis dua 30??C thiab 430 kg ntawm ethyl cawv ntxiv, ces 500 1 ntawm distillate yog sau txog li 80??C hauv qab nqus. Tom qab ua tiav cov distillation cov sib tov yog txias rau ib tug kub ntawm 25-30??C, (cov ntsiab lus dej yog max. 10 w%, nyob rau hauv cov nqe lus ntawm tus nqi kiag li yog hais txog 32 kg), thiab 550 kg ntawm ethyl cawv, Tom qab ntawd 170 kg ntawm 30% hydrochloric ethyl cawv yog ntxiv thiab cov tshuaj tiv thaiv sib tov yog rhuab mus rau reflux rau approx. 2 teev. Thaum cov esterification tiav 800 1 ntawm cov kuab tshuaj yog distilled tawm mus txog 80??C, nyob rau hauv lub nqus tsev vacuum. Ntxiv 800 1 ntawm ethyl cawv ntxiv thiab ntxiv 750-800 1 ntawm cov kuab tshuaj yog distilled tawm mus txog 80??C, nyob rau hauv lub tshuab nqus tsev. Rau cov seem uas tau txais 700 kg ntawm acetonitrile yog ntxiv thiab 140 1 ntawm distillate yog sau txog li 80??C nyob rau hauv lub nqus tsev vacuum. Lub tshuab nqus tsev yog nres los ntawm kev qhia nitrogen thiab cov tshuaj yog txias rau qhov kub ntawm 0-(-)5??C. Cov crystals tau txais yog centrifuged, ntxuav nrog 100 kg ntawm acetonitrile nyob rau hauv ob feem thaum lub sij hawm uas kub yog khaws cia ntawm 0-(-)5??C. Cov khoom tau yog qhuav rau qhov hnyav tas li ntawm 6O0C. Hauv qhov no, 90 kg ntawm cov khoom npe tau txais. Yield: 40%. Melting point: 173-1760C. |
