飞野俊之汉化合集:依巴斯汀 [CAS:90729-43-4]合成路线图解??有机化学网

药物详细合成路线

Chemical Name： 4-tert-Butyl-4-[4-(diphenylmethoxy)piperidin-1-yl]butyrophenone
　　　　　　4-Diphenylmethoxy-1-[3-(4-tert-butylbenzoyl)propyl]piperidine Generic Name： 依巴斯汀;Ebastine Other Names： Ebastine;RP-64305;LAS-W-090;W-090;Evastel;No-Sedat;Kestine;Bastel;Ebastel CAS： 90729-43-4 Formula： C₃₂H₃₉NO₂ Mole Weight： 469.67313 structure： Company： Almirall Prodesfarma (Originator), Boryung (Licensee), Dainippon Pharmaceutical (Licensee), High Noon Labs. (Licensee), Meiji Seika (Licensee), Nycomed Pharma (Licensee) Usage： Allergic Skin Disorders, Treatment for, Antiallergy/Antiasthmatic Drugs, Asthma Therapy, DERMATOLOGIC DRUGS, Drugs for Allergic Rhinitis, RESPIRATORY DRUGS, Treatment of Upper Respiratory Tract Disorders, Urticaria, Treatment for, Histamine H1 Antagonists Route 1 This compound can be obtained by two related routes:1) Condensation of 4-hydroxypiperidine (I) with p-tert-butyl-omega-chlorobutyrophenone (II) in hot methyl isobutyl ketone in presence of sodium bicarbonate gives 1-[3-(4-tert-butylbenzoyl)propyl]-4-hydroxypiperidine (III), which reacts with diphenylmethyl bromide (IV) in methyl isobutyl ketone to give ebastine.2) 4-Diphenylmethoxypiperidine (VI), obtained by alkaline hydrolysis of 1-ethoxycarbonyl-4-diphenyl-methoxypiperidine (V) was reacted with p-tert-butyl-omega-chlorobutyrophenone (II) to give ebastine. Intermediates: Serial No. 3,5-dichlorobenzaldehyde (I) N-[(E)-(3,5-dichlorophenyl)methylidene]-N-methylamine (II) (3,5-dichlorophenyl)-N-methylmethanamine (III) 5,8-dimethoxy-3,4-dihydro-2(1H)-naphthalenone (IV) 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid (V) 2-(acetamido)-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid (VI) Reference 1:     Spickett, R.G.W.; Moragues, J.; Prieto, J.; Vega, A. (Fordonal S.A.); Piperidine derivs. EP 0134124B; US 4550116 . Reference 2:     Moragues, J.; Roberts, D.J.; EBASTINE. Drugs Fut 1990, 15, 7, 674.