(5a,11b)-11-[4-(dimethylamino)phenyl]-5,17-dihydroxy-19-desmethylandrost-9-en-3,20-dionebis(1, preparation of 2-ethylene glycol) cyclic acetal_industrial additives

background and overview^[1]

(5a,11b)-11-[4-(dimethylamino)phenyl]-5,17-dihydroxy-19-desmethylandrosten-9-en-3,20-dionebis (1,2-ethylene glycol) cyclic acetal is an intermediate of ulipristal acetate. ulipristal acetate is a progesterone agonist/antagonist whose main function is to inhibit or delay ovulation. ulipristal acetate is a selective progesterone receptor modulator that has antagonistic and partial agonistic effects on progesterone receptors.

preparation^[1]

the first step: oxidation reaction of 3-methoxy-19-norpregn-1,3,4(10) and 17(20)-tetraene to produce 3-methoxy-19-norpregnant meprogesterone-1,3,5(10)-triene-17α;

second step: reduction reaction of 3-methoxy-19-norpregest-1,3,5(10)-triene-17α and 20α-diol to produce 3-methoxy- 19-norpregest-2,5(10)-diene-17α,20α-diol;

the third step: acidify 3-methoxy-19-norpregest-2,5(10)-diene-17α,20α-diol and oxalic acid to obtain 17α,20α-dihydroxy- 19-nor-5(10)-pregnen-3-one;

step 4: 17α,20α-dihydroxy-19-nor-5(10)-pregnen-3-one is brominated with pyridinium bromide and then debrominated to obtain 17α,20α- dihydroxy-19-norpregest-4,9-dien-3-one;

step 5: oxidize 17α,20α-dihydroxy-19-norpregest-4,9-dien-3-one in dimethyl sulfoxide with ethylene glycol chlorine to obtain the corresponding 17α- hydroxy-19-norpregest-4,9-diene-3,20-dione;

step 6: protect 17α-hydroxy-19-norpregest-4,9-diene-3,20-dione with ethylene glycol diketal to react to generate 3,3,20,20 -bis(ethylenedioxy)-19-norpregest-5(10),9(11)-diene-17α-ol;

step 7: use m-chloroperoxybenzoic acid to dissolve 3,3,20,20-bis(ethylenedioxy)-19-norpregest-5(10),9(11)-di oxygen-17α-ol is oxidized to 5α, 10α-epoxy-3,3,20,20-lonmon titanium dioxide r996 bis(ethylenedioxy)-19-norpregest-9 acrylic resin (11)- en-17α-ol;

step 8: under the catalysis of cuprous chloride, 5α, 10α-epoxy-3,3,20,20-bis(ethylenedioxy)-19-norpregest-9(11 )-en-17α-ol is added to the grignard reagent of 4-dimethylaminobromobenzene for ring opening to obtain (5a,11b)-11-[4-(dimethylamino)phenyl]-5 ,17-dihydroxy-19-desmethylandrosten-9-ene-3,20-dione bis(1,2-ethylene glycol) cyclic acetal.

references

[1] [chinese invention] cn201810485127.5 a new type of ulipristal acetate and its production and manufacturing method