PROCESS FOR PRODUCING BENZOPIRANE DERIVATIVE OF BLOOD PRESSURE LOWERING ACTIVITY

摘要

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) CHEM from 4-cyano-phenol of the formula (I) CHEM which comprises reacting 4-cyano-phenol of the formula (I) with isoprene at 30 - 120 oC 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) CHEM 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) CHEM 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 oC, and then reacting same with 2-pyrrolidone in the presence of alkali-metals at 20 - 100 oC resulting in the end-product of the formula (VI), b.) reacting a compound of the formula (III) CHEM with N-bromo-succinimide in a solvent at 20 - 120 oC to produce 6-cyano-3,4-dihydro-2,2-dimethyl-trans-3-bromo-4-hydroxy-2H-1-benzopyran of the formula (IV) CHEM which is then reacted with 2-pyrrolidone in the presence of alkali-metals at 20 - 100oC resulting in the end-product of the formula (VI). l