Etretinate CAS 54350-48-0

Introduction：Basic information about Etretinate CAS 54350-48-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

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;API;Retinoids
• 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: Solid
• color: Light Yellow to Yellow
• Stability: Light Sensitive
• Major Application: pharmaceutical (small molecule)
• InChI: 1S/C23H30O3/c1-8-26-23(24)14-17(3)11-9-10-16(2)12-13-21-18(4)15-22(25-7)20(6)19(21)5/h9-15H,8H2,1-7H3/b11-9+,13-12+,16-10+,17-14+
• InChIKey: HQMNCQVAMBCHCO-DJRRULDNSA-N
• SMILES: O(C)c1c(c(c(c(c1)C)\C=C\C(=C\C=C\C(=C\C(=O)OCC)\C)\C)C)C
• CAS DataBase Reference: 54350-48-0(CAS DataBase Reference)
• EPA Substance Registry System: Etretinate (54350-48-0)

Safety Information

• WGK Germany: WGK 3
• HS Code: 2918992090
• Storage Class: 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects
• Hazard Classifications: Aquatic Acute 1 Aquatic Chronic 1 Repr. 1A Skin Irrit. 2 STOT SE 3
• 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 910ml of dimethylformamide and treated with cooling at 5°C to 10°C within 20minutes with 17.5 g of a suspension of sodium hydride (about 50% byweight) in mineral oil. The mixture is stirred for 1 hour at about 10°C, thentreated at 5°C to 8°C dropwise with 61.8 g of 3-formylcrotonic acid butylester, heating for 2 hours at 65°C, subsequently introduced into 8 liters of icewater, and, after the addition of 300 g of sodium chloride, thoroughlyextracted with a total of 18 liters of hexane. The extract is washed 5 timeswith 1 liter of methanol/water (6:4 parts by volume) each time and 2 timeswith 1.5 liter of water each time, dried over sodium sulfate and evaporatedunder 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 theresidue.
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 andtreated 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, thencooled, introduced into 10 liters of ice water and, after the addition of about240 ml of concentrated hydrochloric acid (PH 2-4), thoroughly extracted witha total of 9 liters of methylene chloride. The extract is washed with about 6liters of water to neutrality, dried over calcium chloride and evaporated underreduced pressure. The residue is taken up in 700 ml of hexane. Theprecipitated 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 of128 g of ethyl iodide and 128 g of potassium carbonate, the solution is stirredunder 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 ofpetroleum 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 estercrystallizing 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 thetreatment of psoriasis. Its use in pregnant women has resulted in major foetalabnormalities. The manufacturer's information emphasizes that the drug isteratogenic and must not be given to women who are pregnant, and thatcontraceptive measures must be maintained for at least two years afterdiscontinuation of treatment. In some countries, blood banks are advised not toaccept 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