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AssigneeSun Pharmaceutical Industries Limited
InventorsPeriyandi Nagarajan, Kilaru Srinivasu, Thennati Rajamannar
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The present invention provides a process for preparation of 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran car-bonitrile comprising reacting a compound of formula IVa, in the presence of a base with a compound of formula RX, wherein R is selected from alkyl, alkenyl, aryl and heteroaryl which may be optionally substituted with electron withdrawing groups and X is selected from F, Cl, Br, I, CN, OTf and OR1, wherein Tf represents trifluoromethanesulfonyl group, and R1 is optionally substituted alkyl, Z is a cyano group or a group that may be converted to a cyano group; further wherein RX is selected such that an intermediate ether derivative, a compound of formula Va formed from said reaction cyclizes to a compound of formula VI, and where Z is not a cyano group, conversion of the group Z in the compound of formula VI to a cyano group to form 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile. The present invention also provides novel ether compound, a compound of formula Va and a process for preparation thereof.
(S)-(+)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile or Escitalopram with chiral purity greater than 99.8% obtained in more than 50% yield based on (S)-(−)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile or an equivalent precursor thereof, without chiral chromatographic separation of (±)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran carbonitrile or its precursors.
Dependencies are inferred from the claim text.