p-Toluenesulfonic acid → HCID 70614944, compound

HRID 1834955Notes

Reaction equation

HRID 1834955 reaction equation
[H][H].C[C@@H]1C=C2[C@](COC3CCCCO3)(CC[C@H](O)C2)[C@@H]2[C@@H]1[C@H]1[C@@](CC2)(C)[C@@H](O)CC1.C[C@@H]1C[C@@H]2[C@](COC3CCCCO3)(CC[C@H](O)C2)[C@@H]2[C@@H]1[C@H]1[C@@](CC2)(C)[C@@H](O)CC1.C[C@@H]1[C@@H]2[C@](CO)(CC[C@H](O)C2)[C@@H]2[C@H]([C@H]3[C@@](CC2)(C)C(=O)CC3)C1.[OH:84][CH2:85][C@@:86]12[C@@H:103]3[C@H:94]([C@H:95]4[C@@:99]([CH2:101][CH2:102]3)([CH3:100])[C:98](=[O:104])[CH2:97][CH2:96]4)[CH2:93][CH2:92][C:91]1=[CH:90][C:89](=[O:105])[CH2:88][C@@H:87]2[CH3:106].C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(O)C.C1C=CC=CC=1.C(O)CO>[OH:84][CH2:85][C@@:86]12[C@@H:103]3[C@H:94]([C@H:95]4[C@@:99]([CH2:101][CH2:102]3)([CH3:100])[C:98](=[O:104])[CH2:97][CH2:96]4)[CH2:93][CH2:92][C@H:91]1[CH2:90][C:89](=[O:105])[CH2:88][C@@H:87]2[CH3:106]

Participants

11

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 22801511HCID 22801511, compoundHCID 22801512HCID 22801512, compoundHCID 7058400819-Hydroxy1alpha-methyl-4-androstene-3,17-dioneHCID 70614637HCID 70614637, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 70614944HCID 70614944, compound

Reagents, catalysts & solvents 4

HCID 174Ethylene GlycolSolventHCID 241BenzeneSolventHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

Hydrogenation of 19-hydroxy-5-androstenes by means of 10% palladium on charcoal results in good yields of the corresponding 19-hydroxy-5α-androstanes. Suitable steroid substrates which fulfill the 5-ene requirement for stereoselectivity during the reduction include 3β,19-dihydroxy-5-androstenes, 19-hydroxy-5-androsten-3-ones, 19-hydroxy-5-androsten-3-one 3-cyclic ethyleneketal and 3-alkoxy-3,5-androstadien-19-ols. Typical reduction conditions utilize 2-10parts of the steroid substrate to 1 part catalyst with methanol or ethanol as solvent and hydrogen pressures ranging from 1 to 3 atmospheres. In this manner 1β,17α-dimethyl-5-androstene-3β,17β,19-triol, 7α-methyl-19-tetrahydropyranyloxy-5-androsten-3β,17β-diol and 6α-methyl-3β,19-dihydroxy-5-androsten-17-one are reduced to 1β,17α-dimethyl-5α-androstane-3β,17β,19-triol, 7α-methyl-19-tetrahydropyranyloxy-5α-androstan-3β,17β-diol and 6α-methyl-3β,19-dihydroxy-5α-androstan-17-one, respectively. 19-Hydroxy-1α-methyl-4-androstene-3,17-dione is converted to its cyclic ethyleneketal by heating at reflux temperatures with p-toluenesulfonic acid and ethyleneglycol in benzene. The ketal which forms is then reduced and hydrolyzed to form 19-hydroxy-1α-methyl-5α-androstan-3,17-dione. 17β,19-Di(trimethylsiloxy)-4-androsten-3-one can be converted to the methyl enol ether by the action of trimethylorthoformate, p-toluenesulfonic acid and methanol in tetrahydrofuran. The 3-methoxy-3,5-diene which forms is then catalytically reduced to yield 17β,19-di(trimethylsiloxy)-5α-androstan-3-one. The ethylenol ether of 19-hydroxy-4-androsten-3,17-dione acetate can also be reduced to yield 19-hydroxy-5α -androstane-3,17-dione acetate.

Workup

  1. temperatureby heating

Sources & evidence

ORD record
ord-ccc7cfd754974ed29871f5fab0281070
Source dataset
uspto-grants-1978_01
Patent number
US04071625

Reaction notes

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