89778-27-8
- Product Name:Toremifene Citrate
- Molecular Formula:C26H28ClNO.C6H8O7
- Purity:99%
- Molecular Weight:598.093
Product Details;
CasNo: 89778-27-8
Molecular Formula: C26H28ClNO.C6H8O7
Appearance: White or almost white powder
Buy High Quality Toremifene Citrate, Factory Sells 89778-27-8 Cheap Price
- Molecular Formula:C6H8O7*C26H28ClNO
- Molecular Weight:598.093
- Appearance/Colour:White or almost white powder
- Melting Point:158-164oC
- Refractive Index:1,416-1,418
- Boiling Point:535.1 °C at 760 mmHg
- Flash Point:277.4 °C
- PSA:144.60000
- Density:1.045 g/cm3
- LogP:4.96650
Toremifene citrate(Cas 89778-27-8) Usage
Description |
Toremifene (citrate) is an orally bioavailable selective estrogen receptor modulator (SERM) that evokes tissue-dependent effects similar to that of tamoxifen . It has been shown to block estrogen-stimulated growth of MCF-7 breast cancer cells grown in tissue culture, to inhibit ovariectomy-induced bone loss in rats, and to stimulate endometrial growth similar to that of tamoxifen. |
Chemical Properties |
White-to-Off-White Solid |
Originator |
Fareston,Orion Corporation,Finland |
Uses |
An antiestrogen and antineoplastic. Nonsteroidal antiestrogen structurally similar to Tamoxifen. Toremifene, 2-[4-[(1Z)-4-chloro-1,2-diphenyl-1-butenyl]phenoxy]-N,N-dimethylethanamine(Fareston), differs structurally fromtamoxifen only by having a chloroethyl group (rather than anethyl group) attached to the triphenylethylene structure. Asmight be expected, the pharmacological actions of toremifeneand tamoxifen are quite similar. Toremifene is also a SERM,with estrogen antagonist action in breast tissue but agonist actionin the endometrium, on bone tissue, and on serum lipidprofiles. Recent clinical data indicate that the incidence ofendometrial cancer is lower with toremifene use than with tamoxifen. Toremifene is used in the treatment of metastaticbreast cancer in postmenopausal women. |
Manufacturing Process |
The reaction is performed under dry conditions. 2.1 g of lithium aluminum hydride and 50 ml of dry tetrahydrofuran are placed in a flask. Then 13.2 g of cinnamaldehyde in 50 ml of dry tetrahydrofuran are added while stirring and keeping the temperature at 25°-35°C. The stirring is continued for another 30 min at room temperature. Then 26.9 g of 4-[2-(N,N-dimethylamino)- ethoxy]benzophenone in 70 ml of dry tetrahydrofuran are added while stirring. The temperature is kept at 35°-45°C during the addition. After stirring for 2 h at 40°C the reaction mixture is poured into 150 ml of 25% ammonium chloride solution, and aluminium hydroxide is precipitated and filtered off. The filtrate is transferred to a separating funnel and the organic layer is separated. The aqueous layer is once again extracted with 60 ml of ethyl acetate. The organic layers are combined and dried over sodium sulfate. The solvent is evaporated. The residue is recrystallized from toluene. The yield is 27.5 g (68%) of 1,2-diphenyl-1-[4-[2-(N,N-dimethylamino)ethoxy]phenyl]- butane-1,4-diol. The reaction is performed under dry conditions. 40.5 g 1,2-diphenyl-1-[4-[2- (N,N-dimethylamino)ethoxy]phenyl]butane-1,4-diol and 150 ml of acetic acid anhydride are placed in a flask. The temperature is raised to 90°C, where it is kept until the primary OH-group is completely acetylated. [4-Acetoxy-1,2-diphenyl-1-[4-[2-(N,N-dimethylamino)ethoxy]phenyl]butan-1-ol is obtained as intermediate; melting point of the (RR, SS)-isomer pair is 97°-99°C. While stirring the reaction mixture, 30 ml of acetyl chloride in 50 ml of acetic acid anhydride are added at 90°C. The stirring is continued at this temperature for 2 h. The solvent is evaporated. Then 1 M sodium carbonate solution is added in excess, after which the product is extracted in toluene. The solution is dried over sodium sulfate, and the solvent is evaporated. The yield of the pure isomer mixture (Z:E 2:1) of 4-acetoxy-1,2-diphenyl-1-[4-[2-(N,N_x0002_dimethylamino)ethoxy]-phenyl]-1-butene is quantitative. The4-acetoxy-1,2-diphenyl-1-[4-[2-(N,N-dimethylamino)ethoxy]-phenyl]-1- butene are dissolved in 94% ethanol, after which water and 20% sodium hydroxide solution are added. The mixture is refluxed for 1 h. The solution is neutralized with 2 M hydrochloric acid, after wich the ethanol is evaporated. Water is added into the residue. The product is extracted in ethyl acetate, the ethyl acetate solution is dried and the solvent is avaporated. The product is recrystallized from a mixture of water and methanol. The yield of the pure mixture of the isomers (Z:E 2:1) of 1,2-diphenyl-1-[4-[2-(N,Ndimethylamino)ethoxy]phenyl]-1-buten-4-ol, melting point 93°-100°C, is quantitative. Isolation of the (Z)-isomer as a free base: the mixture of the isomers (Z:E 2:1) of 1,2-diphenyl-1-[4-[2-(N,N-dimethylamino)ethoxy]phenyl]-1-buten-4-ol is recrystallized from toluene, and 15.9 g (41%) of the (Z)-isomer is obtained, melting point 110°-112°C. The reaction is performed under dry conditions. 42.4 g of (Z)-1,2-diphenyl-1- [4-[2-(N,N-dimethylamino)ethoxy]phenyl]-1-buten-4-ol are dissolved in 250 ml of chloroform. Then 23.8 g of thionyl chloride are added dropwise. The mixture is refluxed 3 h. The solvent is evaporated, after which the product is recrystallized from ethyl acetate. The yield of the hydrochloride salt of 4- chloro-1,2-diphenyl-1-[4-[2-(N,N-dimethylamino)ethoxy]-phenyl]-1-butene (Z) is 36.7 g (83%), melting point 194°-196°C. The base can be liberated from the salt with 1 M sodium carbonate solution, after which the base is extracted in toluene. The toluene solution is dried and the solvent is evaporated. The free base, 4-chloro-1,2-diphenyl-1-[4-[2-(N,Ndimethylamino)ethoxy]-phenyl]-1-butene (Z), has melting point 108°-110°C (from acetone). In practice it is usually used as citrate salt (1:1). |
Brand name |
Toremifene is INN and BAN. |
Therapeutic Function |
Antiestrogen, Antineoplastic |
Biochem/physiol Actions |
Toremifene citrate is an oral selective estrogen receptor modulator (SERM). It is used in advanced (metastatic) breast cancer and being evaluated for prevention of prostate cancer. Toremifene citrate is known to increase bone mineral density in prostate cancer patients undergoing androgen deprivation therapy?. |
InChI:InChI=1/C26H28ClNO.C6H8O7/c1-28(2)19-20-29-24-15-13-23(14-16-24)26(22-11-7-4-8-12-22)25(17-18-27)21-9-5-3-6-10-21;7-3(8)1-6(13,5(11)12)2-4(9)10/h3-16H,17-20H2,1-2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/b26-25-;
89778-27-8 Relevant articles
POLYMORPHIC FORM OF TOREMIFENE CITRATE AND PROCESS FOR ITS PREPARATION
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Page/Page column 14, (2011/02/24)
The present invention provides a polymor...
89778-27-8 Process route
- 77-92-9,906507-37-7
citric acid
- 89778-26-7
toremifene
- 89778-27-8
toremifene citrate
Conditions | Yield |
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In acetone; at 20 - 25 ℃; Product distribution / selectivity;
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89778-27-8 Upstream products
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77-92-9
citric acid
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89778-26-7
toremifene
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