The present invention relates to a new industrial process for the synthesis of solvate- free 17a-acetoxy-11ss-[4-(N,N-dimethyl-amino)-phenyl]-19-norpregna-4,9-
diene-3,20-dione [CDB -2914] of formula (I) which is a strong antiprogestogene and antiglucocorticoid agent. The invention also relates to compounds of formula (VII) and (VIII) used as intermediates in the process. The process according to the invention is the following: i) 3-(
ethylene-dioxy)-estra-5(10),9(11)-
diene-17-one of formula (X) is reacted with
potassium acetilyde formed in situ in dry
tetrahydrofuran by known method, ii) the obtained 3-(
ethylene-dioxy)-17a-ethynyl-17ss-hydroxy-estra-5(10),9(11)-
diene of formula (IX) is reacted with phenylsulfenyl
chloride in
dichloromethane in the presence of
triethylamine and
acetic acid, iii) the obtained isomeric mixture of 3-(
ethylene-dioxy)-21-(phenyl-sulfinyl)-19-norpregna-5(10),9(11),17(20),20-tetraene of formula (VIII) is reacted first with
sodium methoxide in
methanol, then with
trimethyl phosphite, iv) the obtained 3-(ethylene-dioxy)-17a-hydroxy-20-methoxy-19-norpregna-5(10),9(11),20-triene of formula (VII) is reacted with
hydrogen chloride in
methanol, then v) the obtained 3-(ethylene-dioxy)-17a-hydroxy-19-norpregna-5(10),9(11l); -diene-20- one of formula (VI) is reacted with
ethylene glycol hi
dichloromethane in the presence of
trimethyl orthoformate and p-toluenesulfonic acid by known method, vi) the obtained 3,3,20,20-bis(ethylene-dioxy)-17a-hydroxy-19-norpregna- 5(10),9(11)-diene of formula (V) is reacted with
hydrogen peroxide in a mixture of
pyridine and
dichloromethane in the presence of hexachloroacetone by known method, vii) the obtained 3,3,20,20-bis(ethylene-dioxy)-17a-hydroxy-5,10-
epoxy-19-norpregn-9(11)-ene of formula (IV), containing approximately a 1:1 mixture of 5a,10a- and 5ss,10ss-epoxides, is isolated from the solution and reacted with a
Grignard reagent obtained from 4-bromo-N,N-dimethyl-
aniline in
tetrahydrofuran.