IES960231A2 - Manufacture of steroids - Google Patents
Manufacture of steroidsInfo
- Publication number
- IES960231A2 IES960231A2 IES960231A IES960231A2 IE S960231 A2 IES960231 A2 IE S960231A2 IE S960231 A IES960231 A IE S960231A IE S960231 A2 IES960231 A2 IE S960231A2
- Authority
- IE
- Ireland
- Prior art keywords
- reaction vessel
- holding tank
- delivery line
- acid
- thiopivalic acid
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 150000003431 steroids Chemical class 0.000 title 1
- JHSXHKMJBWOMRU-UHFFFAOYSA-N 2,2-dimethylpropanethioic s-acid Chemical compound CC(C)(C)C(S)=O JHSXHKMJBWOMRU-UHFFFAOYSA-N 0.000 claims abstract description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 16
- BISFDZNIUZIKJD-XDANTLIUSA-N tixocortol pivalate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CSC(=O)C(C)(C)C)(O)[C@@]1(C)C[C@@H]2O BISFDZNIUZIKJD-XDANTLIUSA-N 0.000 claims abstract description 13
- 229960003114 tixocortol pivalate Drugs 0.000 claims abstract description 13
- 150000001885 cortisol derivatives Chemical class 0.000 claims abstract description 5
- 239000003517 fume Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 7
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 229910001220 stainless steel Inorganic materials 0.000 claims description 3
- 239000010935 stainless steel Substances 0.000 claims description 3
- 150000001886 cortisols Chemical class 0.000 claims description 2
- 230000009977 dual effect Effects 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 abstract description 5
- 229950010765 pivalate Drugs 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 2
- 238000004140 cleaning Methods 0.000 abstract 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 abstract 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Tixocortol pivalate is manufactured on an industrial scale by forming a sodium salt of thiopivalic acid in a closed reaction vessel 1. The sodium salt is then reacted with an appropriate hydrocortisone derivative to form the pivalate. The thiopivalic acid is charged through an inlet line 4 into a container 2 which is housed in an enclosed fume tent 15 with a sealable entry door flap 14 and an outlet 16 to a scrubber. The inlet line 4 is then closed and a vacuum is drawn on the line 5 and a delivery line 20 from the reaction vessel 1. A valve 8 is then opened and the acid is drawn into the vessel 1. When the container 2 is emptied, acetone is used to wash any residual acid and the wash is also drawn into the vessel 1, cleaning the delivery line 20. <Fig.2>
Description
The invention relates to a process for the manufacture of esters of 21-thiol steroids, in particular dihydroxy11β,17α thio-21 dioxo-3,20-pregnene-4-21-pivalate.
Introduction
Dihydroxy-llfl,17a thio-21 dioxo-3,20 pregnene-4-21pivalate is known as Tixocortol Pivalate or J01016. US Patent No. 4,014,909 (Jouveinal) describes this compound and its use as a potent anti-inflammatory agent.
The production of tixocortol pivalate involves the use of 10 chemicals which are potentially hazardous. Because of this, it is difficult to optimise the manufacture of the product on an industrial scale.
This invention is therefore directed towards providing an improved process for manufacturing tixocortol pivalate which will overcome these difficulties.
Statements of Invention
According to the invention, there is provided a process for preparing tixocortol pivalate comprising the steps of: 20 charging a desired quantity of thiopivalic acid from a supply container into a holding tank;
delivering the thiopivalic acid from the holding tank into a closed reaction vessel along a delivery line between the holding tank and the reaction vessel;
OPEN TO PUBLIC INSPECTION
UNDER
SECTION 28 AND RULE 23 jNi N'a nv.....
the holding tank
delivering the solvent from the holding tank along the delivery line into the reaction vessel;
salifying the thiopivalic acid in the reaction vessel;
forming an appropriate derivative of hydrocortisone; and reacting the salt of thiopivalic acid with the hydrocortisone derivative to form tixocortol pivalate.
In a particularly preferred embodiment of the invention, the thiopivalic acid is delivered from the holding tank into the reaction vessel by applying a vacuum to the delivery line to draw the thiopivalic acid through the delivery line into the reaction vessel.
In a preferred embodiment of the invention, the solvent is delivered from the holding tank into the reaction vessel by applying a vacuum to the delivery line to draw the solvent through the holding tank and delivery line into the reaction vessel.
Preferably, the holding fitted with a scrubber. tank is located in a fume tent In one embodiment acetone. of the invention, the solvent is In one embodiment of the invention, the salt of thiopivalic acid is a sodium salt. In this case, the
thiopivalic acid may be salified by addition of sodium methoxide.
In one embodiment of the invention, the holding tank inlet/outlet parts are fitted with a dual valve delivery system.
In a preferred arrangement, the delivery line along which the thiopivalic acid and acetone is delivered is a stainless steel pipe.
The invention also provides tixocortol pivalate whenever manufactured by the process of the invention.
Detailed Description
The invention will be more clearly understood from the following description thereof, given by way of example only, with reference to the accompanying drawings, in which:Fig. 1 is a diagrammatic view of a holding tank used in the process of the invention; and
Fig. 2 is a diagrammatic view of apparatus used in the process of the invention.
Tixocortol pivalate is manufactured by a process according to the invention by forming a salt, in this case a sodium salt of thiopivalic acid in a closed reaction vessel 1. The sodium salt of thiopivalic acid is then reacted with an appropriate hydrocortisone derivative especially hydrocortisone-21-mesylate to form tixocortol pivalate.
Thiopivalic acid is charged into a holding tank 2 through one of three ports 3, 4, 5 which are each fitted with a valve 6, 7, 8 and camlock 9, 10, 11 respectively. The container 2 is housed in an enclosed fume tent 15 having
a sealable entry door flap 14 and an outlet 16 to a scrubber in which any accidental leakage of thiopivalic acid is neutralised. A stainless steel delivery line 20 having valves 21, 22 at either end interconnects the container 2 with the reaction vessel 1.
A desired quantity of thiopivalic acid is charged in the fume tent 15 from a supply drum (not shown) into the container 2 through the inlet line 4 with container vented through line 3. The container 2 is weighed when empty and a required quantity of thiopivalic acid is charged into the container. The inlet line 4 is then closed and a vacuum is drawn on the line 5 and delivery line 20 from the reaction vessel 1. The valve 8 is opened and the thiopivalic acid is drawn into the reaction vessel. When the container is empty, the vacuum is released and a solvent, in this case acetone, is charged into the container 2 through the inlet line 4 to wash any residue of thiopivalic acid from the container 2. A vacuum is then applied to the delivery line 20 connected to the line 5 to draw the acetone through the container 2 and delivery line 20 to purge any thiopivalic acid into the reaction vessel 1. When all the acetone is delivered into the reaction vessel 1, the vacuum is released and the valves 22, 21 are closed.
The thiopivalic acid in the reaction vessel 1 is then salified, in this case by the addition of sodium methoxide. The resultant salt is then reacted with an appropriate hydrocortisone derivative as described above.
The invention provides a highly efficient and safe way of manufacturing Tixocortol Pivalate. There is no possibility of any accidental release of thiopivalic acid which is handled in a highly efficient manner allowing the manufacturing process to be optimised.
The invention is not limited to the embodiments hereinbefore described which may be varied in detail.
Claims (5)
1. A process for preparing tixocortol pivalate comprising the steps of:charging a desired quantity of thiopivalic acid from a supply container into a holding tank? delivering the thiopivalic acid from the holding tank into a closed reaction vessel along a delivery line between the holding tank and the reaction vessel; charging a solvent into the holding tank; delivering the solvent from the holding tank along the delivery line into the reaction vessel; salifying the thiopivalic acid in the reaction vessel; forming an appropriate derivative of hydrocortisone; and reacting the salt of thiopivalic acid with the hydrocortisone derivative to form tixocortol pivalate.
2. A process as claimed in claim 1 wherein the thiopivalic acid is delivered from the holding tank into the reaction vessel by applying a vacuum to the delivery line to draw the thiopivalic acid through the delivery line into the reaction vessel.
3. A process as claimed in claim 1 or 2 wherein the solvent is delivered from the holding tank into the reaction vessel by applying a vacuum to the delivery line to draw the solvent through the holding tank and 5 delivery line into the reaction vessel.
4. A process as claimed in any preceding claim wherein the holding tank is located in a fume tent fitted with a scrubber, preferably the solvent is acetone, preferably the salt of thiopivalic acid is a sodium 10 salt, preferably the thiopivalic acid is salified by addition of sodium methoxide, preferably the holding tank inlet/outlet ports are fitted with a dual valve delivery system, preferably the delivery line along which the thiopivalic acid and acetone is delivered 15 is a stainless steel pipe.
5. Tixocortol pivalate whenever prepared by a process as claimed in any preceding claim.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IES960231 IES68868B2 (en) | 1996-03-20 | 1996-03-20 | Manufacture of steroids |
| GB9606017A GB2311290A (en) | 1996-03-20 | 1996-03-22 | Manufacture of steroids |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IES960231 IES68868B2 (en) | 1996-03-20 | 1996-03-20 | Manufacture of steroids |
| GB9606017A GB2311290A (en) | 1996-03-20 | 1996-03-22 | Manufacture of steroids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES960231A2 true IES960231A2 (en) | 1996-07-24 |
| IES68868B2 IES68868B2 (en) | 1996-07-24 |
Family
ID=26308974
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IES960231 IES68868B2 (en) | 1996-03-20 | 1996-03-20 | Manufacture of steroids |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2311290A (en) |
| IE (1) | IES68868B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2689806T3 (en) * | 2013-09-25 | 2018-11-15 | Société Anonyme Monégasque D'etudes Thérapeutiques Vétérinaires-Somet | Mineral salt of the pivotal acid as intermediate, its synthesis procedure and synthesis procedure of thixocortol pivalate |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2231374B1 (en) * | 1973-05-30 | 1976-10-22 | Jouveinal Sa | |
| FR2442856A1 (en) * | 1978-12-01 | 1980-06-27 | Sipsy | PROCESS FOR THE PREPARATION OF STEROIDS |
-
1996
- 1996-03-20 IE IES960231 patent/IES68868B2/en not_active IP Right Cessation
- 1996-03-22 GB GB9606017A patent/GB2311290A/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| GB2311290A (en) | 1997-09-24 |
| GB9606017D0 (en) | 1996-05-22 |
| IES68868B2 (en) | 1996-07-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |