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| | Etretinate Basic information |
| Product Name: | Etretinate | | Synonyms: | 2,4,6,8-nonanetetraenoicacid,9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl;3,7-dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonanetetraenoicaci;all-trans-ethylester;(2E,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonanetetraenoic acid ethyl ester;(2E,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid ethyl;(2E,4E,6E,8E)-9-(4-Methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid ethyl ester;Acitretin Related Compound B (20 mg) (ethyl (all-E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoate);Acitretin Related CoMpound B | | CAS: | 54350-48-0 | | MF: | C23H30O3 | | MW: | 354.48 | | EINECS: | 259-119-3 | | Product Categories: | Aromatics Compounds;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Retinoids;API | | Mol File: | 54350-48-0.mol |  |
| | Etretinate Chemical Properties |
| Melting point | 104-1050C | | Boiling point | 447.69°C (rough estimate) | | density | 1.0304 (rough estimate) | | refractive index | 1.5480 (estimate) | | storage temp. | Sealed in dry,2-8°C | | solubility | Chloroform (Slightly), DMSO (Slightly, Sonicated), Ethyl Acetate (Slightly) | | form | neat | | color | Light Yellow to Yellow | | Stability: | Light Sensitive | | CAS DataBase Reference | 54350-48-0(CAS DataBase Reference) | | EPA Substance Registry System | Etretinate (54350-48-0) |
| HS Code | 2918992090 | | Hazardous Substances Data | 54350-48-0(Hazardous Substances Data) | | Toxicity | LD50 in mice (1 day): >4000 mg/kg i.p. (Bollag); LD50 (20 day) in mice, rats (mg/kg): 1176, >2000 i.p.; >2000, >4000 orally (Kamm) |
| | Etretinate Usage And Synthesis |
| Chemical Properties | Crystalline Solid | | Originator | Tigason,Roche,UK,1981 | | Uses | Aromatic analog of Retinoic Acid. Immunomodulator. Antipsoriatic. | | Definition | ChEBI: Etretinate is a retinoid, an enoate ester and an ethyl ester. It has a role as a keratolytic drug. | | Manufacturing Process | 228 g of 5-(4-methoxy-2,3,6-trimethylphenyl)-3-methyl-penta-2,4-diene-1-
triphenylphosphonium bromide are introduced under nitrogen gassing into 910
ml of dimethylformamide and treated with cooling at 5°C to 10°C within 20
minutes with 17.5 g of a suspension of sodium hydride (about 50% by
weight) in mineral oil. The mixture is stirred for 1 hour at about 10°C, then
treated at 5°C to 8°C dropwise with 61.8 g of 3-formylcrotonic acid butyl
ester, heating for 2 hours at 65°C, subsequently introduced into 8 liters of ice
water, and, after the addition of 300 g of sodium chloride, thoroughly
extracted with a total of 18 liters of hexane. The extract is washed 5 times
with 1 liter of methanol/water (6:4 parts by volume) each time and 2 times
with 1.5 liter of water each time, dried over sodium sulfate and evaporated
under reduced pressure to leave 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-
dimethyl-nona-2,4,6,8-tetraen-1-oic acid butyl ester, MP 80°C to 81°C as the
residue.
125.8 g of 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-
tetraen-1-oic acid butyl ester are introduced into 2,000 ml of abs. ethanol and
treated with a solution of 125.8 g of potassium hydroxide in 195 ml of water.
The mixture is heated to boiling under nitrogen gassing for 30 minutes, then
cooled, introduced into 10 liters of ice water and, after the addition of about
240 ml of concentrated hydrochloric acid (PH 2-4), thoroughly extracted with
a total of 9 liters of methylene chloride. The extract is washed with about 6
liters of water to neutrality, dried over calcium chloride and evaporated under
reduced pressure. The residue is taken up in 700 ml of hexane. The
precipitated 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-
tetraen-1-oic acid melts at 228°C to 230°C.
60 g of 9-(4-methoxy -2,3,6-trimethylphenyl )-3,7-dimethyl-nona-2,4,6 8-
tetraen-1-oic acid are dissolved in 1,000 ml of acetone. After the addition of
128 g of ethyl iodide and 128 g of potassium carbonate, the solution is stirred
under nitrogen gassing for 16 hours at 55°C to 60°C and subsequently
evaporated under reduced pressure. The residue is dissolved in 1,300 ml of
petroleum ether (BP 80°C to 105°C). The 9-(4-methoxy-2,3,6-
trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oic acid ethyl ester
crystallizing out at -20°C, melts at 104°C to 105°C. | | Brand name | Tegison (Roche);Ro 10-9359;Tigasan. | | Therapeutic Function | Antipsoriatic, Antitumor | | World Health Organization (WHO) | Etretinate, a retinol derivative, was introduced in 1981 for the
treatment of psoriasis. Its use in pregnant women has resulted in major foetal
abnormalities. The manufacturer's information emphasizes that the drug is
teratogenic and must not be given to women who are pregnant, and that
contraceptive measures must be maintained for at least two years after
discontinuation of treatment. In some countries, blood banks are advised not to
accept as donors persons who have taken etretinate within the previous year. |
| | Etretinate Preparation Products And Raw materials |
| Raw materials | Iodoethane-->3-Formyl crotonic acid butyl ester-->Potassium carbonate-->Potassium hydroxide-->Sodium hydride-->Triphenylphosphine hydrobromide-->2-Butenoic acid, 4-hydroxy-3-methyl-, ethyl ester, (2E)--->13-cis-Etretinate-->(2E,4E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methylpenta-2,4-dien-1-ol-->BONIYDFKKJJFBB-CDKJVOIVSA-N-->(E)-(4-methoxy-2,3,6-trimethylphenyl)-3-buten-2-one-->(2E,4E)-5-(4-methoxy-2,3,6-trimethylphenyl)-3-methylpenta-2,4-dienal-->TRIETHYL 3-METHYL-4-PHOSPHONOCROTONATE-->Ethynyl methyl vinyl carbinol-->ETHYL 3-METHYL-4-OXOCROTONATE-->2,3,5-TRIMETHYLANISOLE-->4-METHOXY-2,3,6-TRIMETHYL-BENZALDEHYDE-->(E)-Ethyl 4-Bromo-3-methyl-2-butenoate |
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