ChemicalBook CAS DataBase List 2-((3R,5R)-3,5-bis(tert-butyldiMethylsilyloxy)cyclohexylidene)ethanol

2-((3R,5R)-3,5-bis(tert-butyldiMethylsilyloxy)cyclohexylidene)ethanol synthesis

7synthesis methods

Product Name:2-((3R,5R)-3,5-bis(tert-butyldiMethylsilyloxy)cyclohexylidene)ethanol
CAS Number:139356-37-9
Molecular formula:C20H42O3Si2
Molecular Weight:386.72

(3R-trans)-[3,5-Bis[[(1,1-diMethylethyl)diMethylsilyl]oxy]cyclohexylidene]-acetic Acid Ethyl Ester

139356-36-8
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2-((3R,5R)-3,5-bis(tert-butyldiMethylsilyloxy)cyclohexylidene)ethanol

139356-37-9
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Yield:139356-37-9 95%

Reaction Conditions:

with diisobutylaluminium hydride in toluene at -78; for 1 h;

Steps:

[0179] For example, compound a is esterified and the hydroxyl groups are protected to result in compound b (p-TsOH, MeOH, rt, 24 h, 92%; TBDMSCl, TEA, DMF, rt, 18 h, 70%). The thioimidazolide, c, is prepared through reaction of b with 1,1 '-thiocarbonyl-diimidazole in methylene chloride (60 h, rt, 90%). Radical deoxygenation of c with tributyltin hydride in the presence of azobisisobutyronitrile (AIBN) produces the desoxy-ester, d (Bu₃SnH, AIBN, toluene, 80 °C, 2 h, 90%). Ester d is reduced to the alcohol, e (DIBAL-H, toluene, -78 °C, 2 h, 60%), which then undergoes oxidation to form cyclohexanone derivative f (saturated NaI0₄ in water, MeOH, 0 °C, 30 min, 78%), Reaction of f with ethyl (trimethylsilyl)acetate in the presence of lithium diisopropylamide (LDA) in THF (-78 °C, 2 h, 86%) produces the cyclohexyldiene ester, g. The latter is reduced to the allylic alcohol, h (DIBAL-H, toluene, -78 °C, 1 h, 78-95%), which is converted to chloride i by reaction with the complex made from N-chlorosuccinimide and dimethyl sulfide (-25 °C, then 0 °C, 80%). This chloride is treated with lithium diphenylphosphideO °C (-78 °C, 30 min), followed by oxidation with hydrogen peroxide, to form compound j. Compound j is partially deprotected to form compound k, which is dehydroxylated as described for compound c, to result in compound m. Compound m can react with a ketone precursor by methods described herein to form the 19-nor prodrugs of the invention.

References:

WO2011/88209,2011,A2 Location in patent:Page/Page column 59-60