PROCESS FOR PRODUCING BENZOPIRANE DERIVATIVE OF BLOOD PRESSURE LOWERING ACTIVITY

• Main Authors: TIMAR,TIBOR,HU, GALAMB,VILMOS,HU, ISTVAN,ZOLTANNE,HU, ESZENYI,TIBOR,HU, SEBOEK,PETER,HU, NAGYNE CSAKI,ERIKA,HU, FAZEKAS,LAJOSNE,HU, KOVACH,ALMOSNE,HU
• Format: Patent
• Language: English
• Published: 28.06.1993
• Edition: 5
• Subjects: APPARATUS THEREFOR; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The invention relates to a process for the preparation of (+/-)-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidinyl)- 2H-1-benzo py ran-3-ole of the formula (VI) from 4-cyano-phenol of the formula (I) which comprises reacting 4-cyano-phenol of the formula (I) with isoprene at 30 - 120 C in a solvent in the presence of alkali-metals and/or catalysts producing 6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran of the formula (II) which is then converted to 6-cyano-2,2-dimethyl-2H-1-benzopyran at 40 - 150 DEG C in a solvent in the presence of a catalyst and/or an oxydating agent or by bromination in the benzyl position and dehydrobromination of the obtained compound of the formula (X) a.) preparing in one step 6-cyano-3,4-dihydro-2,2-dimethyl-3,4-epoxy-2H-1-benzopyran with peracids in a solvent at 0 - 20 C, and then reacting same with 2-pyrrolidone in the presence of alkali-metals at 20 - 100 C resulting in the end-product of the formula (VI), b.) reacting a compound of the formula (III) with N-bromo-succinimide in a solvent at 20 - 120 C to produce 6-cyano-3,4-dihydro-2,2-dimethyl-trans-3-bromo-4-hydroxy-2H-1-benzopyran of the formula (IV) which is then reacted with 2-pyrrolidone in the presence of alkali-metals at 20 - 100C resulting in the end-product of the formula (VI). l