Hydrogen Peroxide → (z)-7-((1r,2s,3r)-3-Hydroxy-2-{3-[hydroxy-(1-propyl-cyclobutyl)-methyl]-phenyl}-5-oxo-cyclopentyl)-hept-5-enoic acid ethyl amide

HRID 9235

Reaction equation

HRID 9235 reaction equation
COC(=O)CCC/C=C\C[C@H]1[C@@H](O)C[C@@H](O[Si](C(C)(C)C)(C)C)[C@@H]1[C:24]1[CH:29]=[CH:28][C:27]([CH:30]([O:37][Si](C(C)(C)C)(C)C)[CH:31]2[CH2:36][CH2:35][CH2:34]CC2)=[CH:26][CH:25]=1.[CH3:46][CH2:47][CH:48](C)[BH-](C(C)CC)C(C)CC.[Li+].C[O:61][C:62](=O)[CH2:63][CH2:64][CH2:65]/[CH:66]=[CH:67]\[CH2:68][C@H:69]1[C:73](=[O:74])[CH2:72][C@@H:71]([O:75][Si](C(C)(C)C)(C)C)[C@@H:70]1C1C=CC(C(O[Si](C(C)(C)C)(C)C)C2CCCCC2)=CC=1.OO.[NH4+:107].[Cl-].[CH2:109]1COC[CH2:110]1>>[CH2:109]([NH:107][C:62](=[O:61])[CH2:63][CH2:64][CH2:65]/[CH:66]=[CH:67]\[CH2:68][C@H:69]1[C:73](=[O:74])[CH2:72][C@@H:71]([OH:75])[C@@H:70]1[C:29]1[CH:24]=[CH:25][CH:26]=[C:27]([CH:30]([OH:37])[C:31]2([CH2:36][CH2:35][CH3:34])[CH2:48][CH2:47][CH2:46]2)[CH:28]=1)[CH3:110]

Participants

7

Reactant 6

HCID 784Hydrogen PeroxideHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 3611392Lithium tri-s-butylborohydrideHCID 69367304(z)-7-((1r,2s,3r)-3-(Tert-butyl-dimethyl-silanyloxy)-2-{4-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-phenyl}-5-oxo-cyclopentyl)-hept-5-enoic acid methyl esterHCID 69367459(z)-7-((1r,2s,3r,5s)-3-(Tert-butyl-dimethyl-silanyloxy)-2-{4-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-phenyl}-5-hydroxy-cyclopentyl)-hept-5-enoic acid methyl ester

Product 1

HCID 11955158(z)-7-((1r,2s,3r)-3-Hydroxy-2-{3-[hydroxy-(1-propyl-cyclobutyl)-methyl]-phenyl}-5-oxo-cyclopentyl)-hept-5-enoic acid ethyl amideYield 93%

Conditions

Temperature
-78 °C

Procedure

Representative procedure for reduction of the C9 ketone: (Z)-7-((1R,2S,3R,5S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-{4-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-phenyl}-5-hydroxy-cyclopentyl)-hept-5-enoic acid methyl ester (6-1). L-selectride (300 μL, 0.3 mmol, 1 M/THF) was added to a −78° C. solution of ketone 5-3 (159 mg, 0.24 mmol) in 12 mL THF. The reaction was stirred for 30 min. at −78° C. and then 3% H2O2 (7 mL) was added. The reaction was stirred for 2 h at room temperature and then was poured into saturated NH4Cl solution. The mixture was extracted with ethyl acetate (3×50 mL) and the combined ethyl acetate solution was washed with brine and then was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (8% ethyl acetate/hexanes) gave the title alcohol (149 mg, 93%).

Workup

  1. stirringThe reaction was stirred for 2 h at room temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×50 mL)
  3. washthe combined ethyl acetate solution was washed with brine
  4. dry with materialwas dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash chromatography on silica gel (8% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-56cee961749d4215a576198071e7b15b
Source dataset
uspto-grants-2006_08
Patent number
US07091231B2

Linked notes

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