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| | Betamethasone 21-acetate Basic information |
| Product Name: | Betamethasone 21-acetate | | Synonyms: | 9alpha-Fluoro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 21-acetate;(11β,16β)-21-(Acetyloxy)-9-fluoro-11,17-dihydroxy-16-Methylpregna-1,4-diene-3,20-dione;BETAMETHASONE ACETATE LINIMENTS;(17R)-16β-Methyl-21-acetoxy-11β,17α-dihydroxy-9α-fluoropregna-1,4-diene-3,20-dione;21-Acetyloxy-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione;Betamethasone Acetate (500 mg);Betamethasone 21-ace;9ALPHA-FLUORO-16BETA-METHYL-11BETA,17ALPHA,21-TRIHYDROXY-1,4-PREGNADIENE-3,20-DIONE 21-ACETATE | | CAS: | 987-24-6 | | MF: | C24H31FO6 | | MW: | 434.5 | | EINECS: | 213-578-6 | | Product Categories: | Intermediates & Fine Chemicals;Pharmaceuticals;Biochemistry;Hydroxyketosteroids;Steroids;Intracellular receptor | | Mol File: | 987-24-6.mol |  |
| | Betamethasone 21-acetate Chemical Properties |
| Melting point | 200-220°C (dec.) | | alpha | D +140° (chloroform) | | Boiling point | 579.4±50.0 °C(Predicted) | | density | 1.0932 (rough estimate) | | refractive index | 1.5980 (estimate) | | storage temp. | Refrigerator | | solubility | Practically insoluble in water, freely soluble in acetone, soluble in ethanol (96 per cent) and in methylene chloride. It shows polymorphism (5.9). | | pka | 12.08±0.70(Predicted) | | form | neat | | color | White to Off-White | | Water Solubility | 30mg/L(25 ºC) | | Merck | 14,1180 | | CAS DataBase Reference | 987-24-6(CAS DataBase Reference) | | EPA Substance Registry System | .beta.-Methasone acetate (987-24-6) |
| Hazard Codes | Xn | | Risk Statements | 40 | | Safety Statements | 22-36 | | WGK Germany | 3 | | HS Code | 2937220000 |
| | Betamethasone 21-acetate Usage And Synthesis |
| Chemical Properties | White Solid | | Originator | Celestone Soluspan,Schering,US,1965 | | Uses | Betamethasone acetate (BA) | | Uses | amino acid, nutrient | | Uses | CORTICOSTEROID | | Definition | ChEBI: Betamethasone acetate is an acetate ester, a steroid ester, a fluorinated steroid, a 17alpha-hydroxy steroid, a 20-oxo steroid, an 11beta-hydroxy steroid, a 3-oxo-Delta(1),Delta(4)-steroid and a tertiary alpha-hydroxy ketone. It is functionally related to a betamethasone. | | Manufacturing Process | The synthesis is long and complex. For brevity, only the last steps are given
here. Refer to the patents cited below for full details.
Preparation of 9α-Bromo-11β,17α,21-Trihydroxy-16β-Methyl-4-Pregnene-3,20-
Dione 21-Acetate: To a mixture of 620 mg of 17α,21-dihydroxy-16β-methyl-
4,9(11)-pregnadiene-3,20-dione 21-acetate and 330 mg of Nbromosuccinimide in 10 ml of dioxane and 3.2 ml of water cooled to 10°C was
added 1.8 ml of cold 1 M aqueous perchloric acid. The mixture was stirred at
15°C for 3 hours. Excess N-bromosuccinimide was destroyed by addition of
aqueous sodium thiosulfate and most of the dioxane was removed in vacuo.
About 30 ml of water was added and crystalline bromohydrin, 9α-bromo-
11β,17α,21-trihydroxy-16β-methyl-4-pregnene-3,20-dione 21-acetate, was filtered, washed with water, and dried in air.
Preparation of 9β,11β-Epoxy-17α-21-Dihydroxy-16β-Methyl-4-Pregnene-3,20-
Dione 21-Acetate: To a stirred solution of 100 mg of the 9α-bromo-
11β,17α,21-trihydroxy-16β-methyl-4-pregnene-3,20-dione 21-acetate in 3 ml
of tetrahydrofuran and 1 ml of methanol under nitrogen was added 1.02 ml of
0.215N methanolic sodium methoxide. After 10 minutes at 25°C, 0.2 ml of
acetic acid was added and the methanol removed in vacuo. The residue was
acetylated with 1.00 ml of pyridine and 0.5 ml of acetic anhydride at 60°C for
70 minutes. The mixture was taken to dryness in vacuo, water added, and the
product extracted into chloroform. The residue was crystallized from etheracetone to give pure 9β,11β-epoxy-17α,21-dihydroxy-16β-methyl-4-pregnene-
3,20-dione 21-acetate.
Preparation of 9α-Fluoro-11β,17α,21-Trihydroxy-16β-Methyl-4-Pregnene-3,20-
Dione 21-Acetate: To a solution of 200 mg of 9β,11β-epoxy-17α,21-dihydroxy-
16β-methyl-4-pregnene-3,20-dione 21-acetate in 2 ml of chloroform and 2 ml
of tetrahydrofuran in a polyethylene bottle at -60°C was added 2 ml of a 2:1
(by weight) mixture of anhydrous hydrogen fluoride and tetrahydrofuran. After
4 hours at -10°C the mixture was cooled to -60°C and cautiously added to a
stirred mixture of 30 ml or 25% aqueous potassium carbonate and 25 ml of
chloroform kept at -5°C. The aqueous phase was further extracted with
chloroform and the latter phase washed with water and dried over magnesium
sulfate. The residue on crystallization from acetone-ether gave pure 9α-fluoro-
11β,17α,21-trihydroxy-16β-methyl-4-pregnene-3,20-dione 21-acetate.
Preparation of 9α-Fluoro-11β,17α,21-Trihydroxy-16β-Methyl-4-Pregnadiene-
3,20-Dione 21-Acetate 100 mg of 9α-fluoro-11β,17α,21-trihydroxy-16β-
methyl-4-pregnene-3,20-dione 21-acetate was treated with selenium dioxide
to produce the corresponding 9α-fluoro-11β,17α,21-trihydroxy-16β-methyl-4-
pregnadiene-3,20-dione 21-acetate. Alternately, Bacillus sphaericus may be
utilized. | | Therapeutic Function | Glucocorticoid |
| | Betamethasone 21-acetate Preparation Products And Raw materials |
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