Dibenzo-18-crown-6 → 1alpha,3beta-dihydroxy-20(S)-{2(R)-hydroxy-3-methylbutyloxy}pregna-5,7,16-triene

HRID 1268538Notes

Reaction equation

HRID 1268538 reaction equation
[Si](O[C@@H]1[C@@]2(C)C(=CC=C3[C@@H]2CC[C@@]2(C)[C@H]3CC=C2[C@@H](O)C)C[C@@H](O[Si](C(C)(C)C)(C)C)C1)(C(C)(C)C)(C)C.CC(C)([O-])C.[K+].C1OCCOC2C(=CC=CC=2)OCCOCCOC2C(=CC=CC=2)OC1.O1[C@H](C(C)C)C1.[Si]([O:84][C@@H:85]1[C@@:110]2([CH3:111])[C:89](=[CH:90][CH:91]=[C:92]3[C@@H:109]2[CH2:108][CH2:107][C@@:106]2([CH3:112])[C@H:93]3[CH2:94][CH:95]=[C:96]2[C@@H:97]([O:99][CH2:100][C@H:101]([OH:105])[CH:102]([CH3:104])[CH3:103])[CH3:98])[CH2:88][C@@H:87]([O:113][Si](C(C)(C)C)(C)C)[CH2:86]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C1(C)C=CC=CC=1>[OH:84][C@@H:85]1[C@@:110]2([CH3:111])[C:89](=[CH:90][CH:91]=[C:92]3[C@@H:109]2[CH2:108][CH2:107][C@@:106]2([CH3:112])[C@H:93]3[CH2:94][CH:95]=[C:96]2[C@@H:97]([O:99][CH2:100][C@H:101]([OH:105])[CH:102]([CH3:104])[CH3:103])[CH3:98])[CH2:88][C@@H:87]([OH:113])[CH2:86]1

Participants

9

Reactant 6

HCID 26541Dibenzo-18-crown-6HCID 2724141Tetrabutylammonium FluorideHCID 7017987(R)-IsopropyloxiraneHCID 120200781alpha,3beta-bis(tert-butyldimethylsilyloxy)-20(S)-hydroxypregna-5,7,16-trieneHCID 229597681alpha,3beta-bis(tert-butyldimethylsilyloxy)-20(S)-{2(R)-hydroxy-3-methyl-butyloxy}pregna-5,7,16-trieneHCID 23665647Potassium tert-butoxide

Product 1

HCID 229597971alpha,3beta-dihydroxy-20(S)-{2(R)-hydroxy-3-methylbutyloxy}pregna-5,7,16-trieneYield 69.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Using 1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-hydroxypregna-5,7,16-triene (71.5 mg, 0.128 mmol), potassium t-butoxide (170 mg, 1.52 mmol), dibenzo-18-crown-6(32.0 mg, 0.0888 mmol), toluene (4.5 ml) and (R)-(−)-1,2-epoxy-3-methylbutane (0.13 ml, 1.24 mmol), alkylation reacion (108° C., 1 hour) and work up were performed by the same procedure as in Example 119, and then the residue was separated by preparative thin layer chromatography (0.5 mm×3, hexane:dichloromethane:ethyl acetate 45:5:2, developed three times) to give a fraction containing 1α,3β-bis(tert-butyldimethylsilyloxy)-20(S)-{2(R)-hydroxy-3-methyl-butyloxy}pregna-5,7,16-triene (26.8 mg). This was deprotected with tetrahydrofuran (1 ml) and 1M tetra-n-butylammonium fluoride solution in tetrahydrofuran (0.4 ml) (reaction temperature 74° C., reaction period 12 hours) and worked up by the same procedure as in Example 119, and then the residue was purified by preparative thin layer chromatography (0.25 mm×1, dichloromethane:ethanol=15:1, developed twice) to give the title compound as a colorless oil (12.0 mg, 23%).

Workup

  1. customthe residue was separated by preparative thin layer chromatography (0.5 mm×3, hexane:dichloromethane:ethyl acetate 45:5:2, developed three times)
  2. customto give a fraction
  3. customthe residue was purified by preparative thin layer chromatography (0.25 mm×1, dichloromethane

Sources & evidence

ORD record
ord-c5428b1c540b47bc8c5092811f3ecc86
Source dataset
uspto-grants-2003_04
Patent number
US06555699B2

Reaction notes

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