DE1593348C3 - Verfahren zur Herstellung von 19-Fluorsteroidepoxyden und 19-Fluor-11,19epoxysteroide - Google Patents
Verfahren zur Herstellung von 19-Fluorsteroidepoxyden und 19-Fluor-11,19epoxysteroideInfo
- Publication number
- DE1593348C3 DE1593348C3 DE19661593348 DE1593348A DE1593348C3 DE 1593348 C3 DE1593348 C3 DE 1593348C3 DE 19661593348 DE19661593348 DE 19661593348 DE 1593348 A DE1593348 A DE 1593348A DE 1593348 C3 DE1593348 C3 DE 1593348C3
- Authority
- DE
- Germany
- Prior art keywords
- group
- fluoro
- hydroxy
- compound
- steroid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
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- 230000008569 process Effects 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000002576 ketones Chemical class 0.000 claims description 8
- 125000001931 aliphatic group Chemical group 0.000 claims description 7
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- 239000001301 oxygen Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims 1
- 125000003700 epoxy group Chemical group 0.000 claims 1
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
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- 239000004157 Nitrosyl chloride Substances 0.000 description 4
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- 125000004185 ester group Chemical group 0.000 description 4
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- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 4
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- 125000005646 oximino group Chemical group 0.000 description 4
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- 239000011591 potassium Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
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- OMIHGPLIXGGMJB-UHFFFAOYSA-N 7-oxabicyclo[4.1.0]hepta-1,3,5-triene Chemical compound C1=CC=C2OC2=C1 OMIHGPLIXGGMJB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 206010067572 Oestrogenic effect Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- NWSBNVVOFKKFNV-UHFFFAOYSA-N chloroform;oxolane Chemical compound ClC(Cl)Cl.C1CCOC1 NWSBNVVOFKKFNV-UHFFFAOYSA-N 0.000 description 3
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- 230000002254 contraceptive effect Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
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- 238000000605 extraction Methods 0.000 description 3
- 239000012025 fluorinating agent Substances 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
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- 239000000543 intermediate Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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- 230000015843 photosynthesis, light reaction Effects 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 208000029422 Hypernatremia Diseases 0.000 description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
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- 229910052783 alkali metal Inorganic materials 0.000 description 2
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- 239000002585 base Substances 0.000 description 2
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
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- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- 238000001035 drying Methods 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- ATYDCSOOXNWKIE-UHFFFAOYSA-N mercury;methanol Chemical compound [Hg].OC ATYDCSOOXNWKIE-UHFFFAOYSA-N 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- ITYJDNHFRZSTJY-UHFFFAOYSA-N methanesulfonyl bromide Chemical compound CS(Br)(=O)=O ITYJDNHFRZSTJY-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- ZEIYBPGWHWECHV-UHFFFAOYSA-N nitrosyl fluoride Chemical compound FN=O ZEIYBPGWHWECHV-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 230000027758 ovulation cycle Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008014 pharmaceutical binder Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- WKFBZNUBXWCCHG-UHFFFAOYSA-N phosphorus trifluoride Chemical compound FP(F)F WKFBZNUBXWCCHG-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- ZRLVQFQTCMUIRM-UHFFFAOYSA-N potassium;2-methylbutan-2-olate Chemical compound [K+].CCC(C)(C)[O-] ZRLVQFQTCMUIRM-UHFFFAOYSA-N 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51469165A | 1965-12-17 | 1965-12-17 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE1593348A1 DE1593348A1 (de) | 1970-07-30 |
| DE1593348B2 DE1593348B2 (de) | 1974-07-18 |
| DE1593348C3 true DE1593348C3 (de) | 1975-03-06 |
Family
ID=24048303
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19661593348 Expired DE1593348C3 (de) | 1965-12-17 | 1966-12-17 | Verfahren zur Herstellung von 19-Fluorsteroidepoxyden und 19-Fluor-11,19epoxysteroide |
| DE19661793794 Pending DE1793794A1 (de) | 1965-12-17 | 1966-12-17 | Pharmazeutische zusammensetzungen |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19661793794 Pending DE1793794A1 (de) | 1965-12-17 | 1966-12-17 | Pharmazeutische zusammensetzungen |
Country Status (9)
| Country | Link |
|---|---|
| BE (1) | BE691320A (enExample) |
| CH (1) | CH587290A5 (enExample) |
| DE (2) | DE1593348C3 (enExample) |
| DK (1) | DK123407B (enExample) |
| FR (2) | FR1511151A (enExample) |
| GB (1) | GB1177648A (enExample) |
| IL (1) | IL27072A (enExample) |
| NL (1) | NL6617739A (enExample) |
| SE (1) | SE348190B (enExample) |
-
1966
- 1966-12-13 GB GB5587466A patent/GB1177648A/en not_active Expired
- 1966-12-16 DK DK653366A patent/DK123407B/da unknown
- 1966-12-16 IL IL2707266A patent/IL27072A/en unknown
- 1966-12-16 BE BE691320D patent/BE691320A/xx unknown
- 1966-12-16 SE SE1727966A patent/SE348190B/xx unknown
- 1966-12-16 FR FR87807A patent/FR1511151A/fr not_active Expired
- 1966-12-16 NL NL6617739A patent/NL6617739A/xx unknown
- 1966-12-17 DE DE19661593348 patent/DE1593348C3/de not_active Expired
- 1966-12-17 DE DE19661793794 patent/DE1793794A1/de active Pending
- 1966-12-19 CH CH1812266A patent/CH587290A5/de not_active IP Right Cessation
-
1967
- 1967-03-16 FR FR99003A patent/FR6920M/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE1593348A1 (de) | 1970-07-30 |
| IL27072A (en) | 1972-07-26 |
| GB1177648A (en) | 1970-01-14 |
| SE348190B (enExample) | 1972-08-28 |
| CH587290A5 (en) | 1977-04-29 |
| DE1793794A1 (de) | 1975-07-31 |
| DK123407B (da) | 1972-06-19 |
| BE691320A (enExample) | 1967-06-16 |
| NL6617739A (enExample) | 1967-06-19 |
| DE1593348B2 (de) | 1974-07-18 |
| FR6920M (enExample) | 1969-05-05 |
| FR1511151A (fr) | 1968-01-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) |