Valisone,Schering,US,1967
Dexamethasone Valerate (Betamethasone Valerate EP Impurity C) is an impurity of Dexamethasone (D298800), which is a glucocorticoid that is used as an anti-inflammatory agent. Dexamethasone regulates T cell survival, growth, and differentiation. Dexamethasone inhibits the induction of nitric oxide synthase.
The valerate is made from betamethasone as a starting material as follows: A
suspension of 9α-fluoro-11β,17α,21-trihydroxy-16β-methylpregna-1,4-diene-
3,20-dione(betamethasone) (2 grams) in sodium dried benzene (500 ml) was
distilled vigorously for a few minutes, toluene-p-sulfonic acid monohydrate (30
mg) and methyl orthovalerate (5 ml) were added and distillation was
continued for 10 minutes. The mixture was then boiled under reflux for 1.5
hours after which time unreacted betamethasone alcohol (400 mg) was
removed by filtration. The benzene solution was treated with solid sodium
.bicarbonate and a few drops of pyridine, filtered and evaporated to dryness
at about 50°C. The residue, in ether, was filtered through grade III basic
alumina (20grams) to remove traces of unreacted betamethasone alcohol, the
ether removed in vacuo and the residue of crude betamethasone 17,21-
methyl orthovalerate was treated with acetic acid (20ml) and a few drops of
water and left overnight at room temperature.
The acetic acid solution was poured into water (100 ml) and extracted with
chloroform. The chloroform extracts were washed in turn with water, saturated
sodium bicarbonate solution and water, dried and evaporated in vacuo. The
residual gum was triturated with ether and a white crystalline solid (1.16
grams) isolated by filtration. Recrystallization from ether (containing a small
amount of acetone)-petroleum ether gave 9α-fluoro-11β,21-dihydroxy-16β-
methyl-17α-valeryloxypregna-1,4-diene-3,20-dione (871 mg) as fine needles.
