US4233121A
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Process for the preparation of 5-halo-6,9 α-oxido-prostaglandin derivatives
Assignee: Chinoin Private Co Ltd
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Filing: 1979-05-21
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Granted: 1980-11-11
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Expires: 1999-05-21
Abstract
Abstract The invention concerns a new process for the preparation of 5-halo-6,9α-oxido-prostaglandin derivatives of the general formula II ##STR1## wherein R 1 represents a hydrogen atom, an alkyl group optionally substituted by aryl, amino, hydroxyl or a halogen atom, an equivalent of a pharmaceutically acceptable organic or inorganic cation or a conventional hydroxyl protecting group; R 2 represents a hydrogen atom, a hydroxyl group or a conventionally protected hydroxyl group; R 3 is a hydrogen atom or a lower alkyl group; R 4 represents a hydrogen atom or a conventional hydroxyl protecting group; R 5 stands for a straight or branched chained alkyl group, optionally containing hetero atom(s) and optionally substituted by a substituted or unsubstituted aryl group, and X stands for a halogen atom, which comprises subsjecting prostaglandin F 2 α derivatives of the general formula I ##STR2##
Inventors
- 👤 Eniko Szebenyi nee Gyori
- 👤 Vera Kovacs nee Mindler
- 👤 Laszlo Redey
- 👤 Agnes Szemos nee Szonyi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 07:57
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/77; C07D307/93; C07D307/935; C07D307/937; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
126 words
A process for the preparation of a 5-halo-6,9α-oxido-prostaglandin derivative of the formula II ##STR6## wherein R 1 is hydrogen alkyl which can be substituted with aryl, amino, hydroxyl or halogen, a pharmaceutically acceptable organic or inorganic cation or a conventional hydroxyl protecting group; R 2 is hydrogen hydroxyl or a conventionally protected hydroxyl group; R 3 is hydrogen or lower alkyl; R 4 is hydrogen or a conventional hydroxyl protecting group; R 5 is straight or branched chain alkyl, which can contain one or more heteroatoms and which can be substituted with a substituted or unsubstituted aryl group, and X is halogen, which comprises subjecting a prostaglandin F 2 α derivative of the formula I ##STR7## to electrochemical oxidation in a protic medium containing halide ions.
Claim 2
Dependent Claim
126 words
A process for the preparation of a 5-halo-6,9α-oxido-prostaglandin derivative of the formula II ##STR6## wherein R 1 is hydrogen alkyl which can be substituted with aryl, amino, hydroxyl or halogen, a pharmaceutically acceptable organic or inorganic cation or a conventional hydroxyl protecting group; R 2 is hydrogen hydroxyl or a conventionally protected hydroxyl group; R 3 is hydrogen or lower alkyl; R 4 is hydrogen or a conventional hydroxyl protecting group; R 5 is straight or branched chain alkyl, which can contain one or more heteroatoms and which can be substituted with a substituted or unsubstituted aryl group, and X is halogen, which comprises subjecting a prostaglandin F 2 α derivative of the formula I ##STR7## to electrochemical oxidation in a protic medium containing halide ions.
Claim 3
Dependent Claim
39 words
The process defined in claim 1 wherein the electrochemical oxidation is carried out in a medium containing water, alkanols, nitriles, organic or inorganic acids or mixtures thereof as a protic solvent, which can contain salts acting as a buffer.
Claim 4
Dependent Claim
22 words
The process defined in claim 2, in which as a protic solvent a lower alkanol, nitrile or a mixture thereof is used.
Claim 5
Dependent Claim
43 words
The process defined in claim 1 for the preparation of a compound of the formula II, wherein X is iodine, which comprises carrying out the electrochemical oxidation in a medium containing water, acetic acid, an alkali metal acetate, and an alkali metal iodide.
Claim 6
Dependent Claim
28 words
The process defined in claim 1 for the preparation of 5-iodo-6,9α-oxido-11α,15α-dihydroxy-13-trans-prostenic acid, which comprises subjecting prostaglandin F 2 α to electrochemical oxidation in a medium containing iodine ions.
Claim 7
Dependent Claim
41 words
The process defined in claim 1 for the preparation of a compound of the formula II, in which X is bromine which comprises carrying out the electrochemical oxidation in a medium containing water, acetonitrile, acetic acid and an alkali metal bromide.
Claim 8
Dependent Claim
29 words
The process defined in claim 1 for the preparation of 5-bromo-6,9α-, 15α-dihydroxy-13-trans-prostenic acid, which comprises subjecting prostaglandin F 2 α to electrochemical oxidation in a medium containing bromide ions.
Claim 9
Dependent Claim
29 words
The process defined in claim 1 which comprises carrying out the electrochemical oxidation in an electrolytic cell, in which the cathode and anode space are separated by a diaphragm.
Claim 10
Dependent Claim
26 words
The process as defined in claim 1 which comprises carrying out the electrochemical oxidation by using as an anode an electrode having a high oxygen overvoltage.
Claim 11
Dependent Claim
24 words
The process as defined in claim 9, in which as an anode having a high oxygen overvoltage, gold, platinum, palladium or titanium is employed.
Claim 12
Dependent Claim
22 words
The process defined in claim 1 wherein the electrochemical oxidation is carried out at a temperature between 0° C. and 80° C.
Claim 13
Dependent Claim
33 words
The process as defined in claim 1 wherein the compound of formula II produced by electrochemical oxidation has one of said protecting groups, said process further comprising splitting off the latter protecting groups.
Claim 14
Dependent Claim
21 words
A process as claimed in claim 1, substantially as hereinbefore described with reference to any one of Examples 1 and 2.
Claim 15
Dependent Claim
109 words
A process for the preparation of a 5-halo-6,9α-oxido-prostaglandin derivative of the formula ##STR8## wherein R 1 is hydrogen, C 1 to C 20 straight or branched alkyl which can be substituted with amino, hydroxyl or halogen, or a pharmaceutically acceptable organic or inorganic cation; R 2 is hydrogen or hydroxyl; R 3 is hydrogen or lower alkyl; R 4 is hydrogen; R 5 is straight or branched chain C 1 to C 20 alkyl; and is halogen, which comprises subjecting a prostaglandin F 2 α derivative of the formula ##STR9## to electrochemical oxidation in an aqueous medium containing ions selected from the group which consist of bromide and iodide.
Claim 16
Dependent Claim
109 words
A process for the preparation of a 5-halo-6,9α-oxido-prostaglandin derivative of the formula ##STR8## wherein R 1 is hydrogen, C 1 to C 20 straight or branched alkyl which can be substituted with amino, hydroxyl or halogen, or a pharmaceutically acceptable organic or inorganic cation; R 2 is hydrogen or hydroxyl; R 3 is hydrogen or lower alkyl; R 4 is hydrogen; R 5 is straight or branched chain C 1 to C 20 alkyl; and is halogen, which comprises subjecting a prostaglandin F 2 α derivative of the formula ##STR9## to electrochemical oxidation in an aqueous medium containing ions selected from the group which consist of bromide and iodide.
Claim 17
Dependent Claim
185 words
A process for the preparation of a 5-halo-6,9α-oxido-prostaglandin derivative of the formula ##STR10## wherein R 1 is hydrogen, C 1 to C 2 straight or branched alkyl which can be substituted with amino, hydroxyl or halogen, a pharmaceutically acceptable organic or inorganic cation or a hydroxyl protecting group selected from the group which consists of tetrahydro pyranyl, alkylsilyl, aromatic or aliphatic acyl or aromatic carbamoyl eliminated by hydrolysis; R 2 is hydrogen hydroxyl or hydroxyl having a hydroxyl protecting group selected from the group which consists of tetrahydro pyranyl, alkylsilyl, aromatic or aliphatic acyl or aromatic carbamoyl eliminated by hydrolysis; R 3 is hydrogen or lower alkyl; R 4 is hydrogen or a hydroxyl protecting group selected from the group which consists of tetrahydro pyranyl, alkylsilyl, aromatic or aliphatic acyl or aromatic carbamoyl eliminated by hydrolysis; R 5 is straight or branched chain C 1 to C 20 alkyl; and X is halogen, which comprises subjecting a prostaglandin F 2 α derivative of the formula ##STR11## to electrochemical oxidation in an aqueous medium containing ions selected from the group which consists of bromide and iodide.
Claim 18
Dependent Claim
185 words
A process for the preparation of a 5-halo-6,9α-oxido-prostaglandin derivative of the formula ##STR10## wherein R 1 is hydrogen, C 1 to C 2 straight or branched alkyl which can be substituted with amino, hydroxyl or halogen, a pharmaceutically acceptable organic or inorganic cation or a hydroxyl protecting group selected from the group which consists of tetrahydro pyranyl, alkylsilyl, aromatic or aliphatic acyl or aromatic carbamoyl eliminated by hydrolysis; R 2 is hydrogen hydroxyl or hydroxyl having a hydroxyl protecting group selected from the group which consists of tetrahydro pyranyl, alkylsilyl, aromatic or aliphatic acyl or aromatic carbamoyl eliminated by hydrolysis; R 3 is hydrogen or lower alkyl; R 4 is hydrogen or a hydroxyl protecting group selected from the group which consists of tetrahydro pyranyl, alkylsilyl, aromatic or aliphatic acyl or aromatic carbamoyl eliminated by hydrolysis; R 5 is straight or branched chain C 1 to C 20 alkyl; and X is halogen, which comprises subjecting a prostaglandin F 2 α derivative of the formula ##STR11## to electrochemical oxidation in an aqueous medium containing ions selected from the group which consists of bromide and iodide.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-11-11 | 1984-05-12 | 1984-11-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-11-11 | 1988-05-12 | 1988-11-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-11-11 | 1992-05-12 | 1992-11-11 | $7700.00 | Window Closed / Lapsed |