Estriol synthesis

13synthesis methods

Product Name:Estriol
CAS Number:50-27-1
Molecular formula:C18H24O3
Molecular Weight:288.38

Estriol, estra-1,3,5(10)-trien-3,16α,17β-triol (28.1.25), is proposed to be synthesized from the methyl ester of estrone (28.1.8). Methyl ester of estrone is reacted with isopropenylacetate in the presence of p-toluenesulfonic acid, forming the corresponding enolacetate (28.1.23). The resulting enolacetate is oxidized to an epoxide using perbenzoic acid. The resulting epoxide (28.1.24) undergoes reduction by lithium aluminum hydride to.

1,3,5[10]-ESTRATRIENE-3,16ALPHA-DIOL-17-ONE

566-76-7
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50-27-1
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$11.00/100mg

Yield:50-27-1 94%

Reaction Conditions:

with methanol;sodium tris(acetoxy)borohydride in 1,4-dioxane at 20 - 25;

Steps:

4

Example: 4: Reduction to 17p-estriol:Preparation of estra-l,3,5,(10)-trien-3,16a,17P -triol; To a 1 : 1 mixture of methanol: dioxane (500ml) in a one litre round bottomed flask, was added 3,16a -Hydroxy-estra-1,3,5 (10)-trien-17-one (22gm, 76.7mmole) and stirred to obtain homogeneous solution. At this point, sodium triacetoxyborohydride (16gm, 76mmole)was added slowly in lots so that the internal temperature does not exceed 20°C. The mixture was stirred for four hours at room temperature (23-25°C) after which another lot of reductant (25gm,l 17mmole)was added in four lots, each lot in one hour interval, after which the reaction mixture concentrated under reduced pressure and dil. HC1 (IN solution ,450ml) was added slowly to the residue and stirred for 10 minutes vigorously. The precipitated solid was filtered and washed with water (2 X 1 10ml) .The solid obtained was suspended in acetone (250ml) and stirred for 10 minutes and filtered to obtain the title compound.Yield : 20.5gm (94%).HPLC Purity : 99.53%]H NMR (400MHz,DMSO +CDC1₃)0.66(3H,s), 1.20-2.8(13H,m), 3.29(lH,m), 3.83(lH,m), 4.57(lH,dd,J=5Hz and 1.2Hz), 4.6(lH,dd,J=5Hz and 1.2Hz), 6.43(1 H,s), 6.50(lH,d,J=8Hz), 7.03(lH,d,J=8.4Hz)

References:

WO2012/32529,2012,A1 Location in patent:Page/Page column 10

79258-14-3 Synthesis