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ChemicalBook CAS DataBase List 5-Iodomethyl 6a,9a-Difluoro-11-hydroxy-16a-methyl-3-oxo-17a-(propionyloxy)-androsta-1,4-diene-17-carbothioate
80474-67-5

5-Iodomethyl 6a,9a-Difluoro-11-hydroxy-16a-methyl-3-oxo-17a-(propionyloxy)-androsta-1,4-diene-17-carbothioate synthesis

7synthesis methods
-

Yield:80474-67-5 75%

Reaction Conditions:

with 2,6-di-tert-butyl-4-methyl-phenol;hydroquinone;sodium iodide in acetone at 60 - 65; for 24 - 48 h;Product distribution / selectivity;

Steps:

1; 2; 3; 4; 5; 6

Examples; Example 1 : preparation ofiodomethyl ester 6 from chloromethyl ester 5; Sodium iodide (4.0 eq) was charged to acetone (20 vol) under stirring. Butylated hydroxytoluene (BHT) (1.0 eq) and hydroquinone (1.0 eq) were added to the stirred suspension of sodium iodide at 25-300C. The reaction mixture was stirred for 30 minutes. Chloromethyl ester 5 (1.0 eq) was added to this stirred suspension and the reaction mixture was refluxed for 24 hours at 60-650C. After completion of the reaction, the product was isolated by distillation of acetone and precipitation by adding 5% w/v solution of NaHCO3. The crude iodomethyl ester 6 was filtered, washed with water (3 x 10 vol) and dried under reduced pressure (-100 mm of Hg) at 55-60°C for 4 hours. Yield: 75-85% w/w. HPLC purity: 96-97%.; The use of hydroquinone and butylated hydroxytoluene gave good reproducibility and consistency with respect to control over the non-polar dimer impurity up to a 50 g scale. The amount of non-polar dimer impurity was not more than 0.5% (earlier this impurity was up to 36%). The results of the study of radical inhibitors and antioxidants are summarised in Table 1.

References:

WO2007/144668,2007,A2 Location in patent:Page/Page column 21; 29-30

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