Hydrogen Peroxide → HCID 46238961, compound

HRID 1485878Notes

Reaction equation

HRID 1485878 reaction equation
COC[O:4][C:5]1[CH:6]=[CH:7][C:8]2[C@@H:9]3[C@@H:17]([CH2:18][CH:19](O)[C:20]=2[CH:21]=1)[C@H:16]1[C@@:12]([CH3:27])([C@@H:13]([O:23]COC)[CH2:14][CH2:15]1)[CH2:11][CH2:10]3.C[C:29]([CH3:32])([O-])[CH3:30].[K+].[CH:34](NC(C)C)([CH3:36])[CH3:35].C([Li])CCC.B(OC)(OC)[O:47][CH3:48].OO>C1COCC1>[CH3:48][O:47][CH2:35][CH2:34][CH2:36][CH2:30][CH2:29][CH2:32][C@@H:19]1[CH2:18][C@@H:17]2[C@H:9]([CH2:10][CH2:11][C@@:12]3([CH3:27])[C@H:16]2[CH2:15][CH2:14][CH:13]3[OH:23])[C:8]2[CH:7]=[CH:6][C:5]([OH:4])=[CH:21][C:20]1=2

Participants

8

Reactant 6

HCID 784Hydrogen PeroxideHCID 7912DiisopropylamineHCID 8470Trimethyl borateHCID 11581610HCID 11581610, compoundHCID 23665647Potassium tert-butoxideHCID 178418339Butyllithium

Product 1

HCID 46238961HCID 46238961, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

(8R,9S,13S,14S,17S)-3,17-bis(methoxymethoxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-ol—To a solution of potassium tert-butoxide (8.87 g, 79.0 mmol) and diisopropylamine (11.2 mL, 79.0 mmol) in 80 mL of anhydrous THF cooled to −78° C. under argon is added n-butyllithium (49.4 mL, 79.0 mmol, 1.6 M in hexane) dropwise. The reaction mixture is stirred at −78° C. for 30-45 minutes. A solution of the compound from a) (5.7 g, 15.8 mmol) in 45 mL of THF is then added dropwise, and the reaction mixture is stirred for 3 hours at −78° C. During the addition of the compound from a), the reaction turns a deep red color. Trimethyl borate (10.6 mL, 94.8 mmol) is then added slowly, and the mixture is warmed to 0° C. and stirred for 2 hours. Hydrogen peroxide (24 mL of a 30% aq. solution) is then added, and the reaction mixture is warmed to room temperature and stirred for a further 1 hour. The reaction is cooled back to 0° C. and carefully quenched with a 10% aq. Na2S2O3 solution (70 ml). The resulting mixture is extracted with EtOAc (2×), and the combined organic extracts are dried (Na2SO4), filtered, and evaporated in vacuo to give a yellow/brown oil. Purification by silica gel column chromatography (256 EtOAc/Hex) affords the title compound as a white solid (3.5 g, 59%).

Workup

  1. stirringthe reaction mixture is stirred for 3 hours at −78° C
  2. additionDuring the addition of the compound from a), the reaction
  3. temperaturethe mixture is warmed to 0° C.
  4. stirringstirred for 2 hours
  5. temperaturethe reaction mixture is warmed to room temperature
  6. stirringstirred for a further 1 hour
  7. temperatureThe reaction is cooled back to 0° C.
  8. customcarefully quenched with a 10% aq. Na2S2O3 solution (70 ml)
  9. extractionThe resulting mixture is extracted with EtOAc (2×)
  10. dry with materialthe combined organic extracts are dried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customto give a yellow/brown oil
  14. customPurification by silica gel column chromatography (256 EtOAc/Hex)

Sources & evidence

ORD record
ord-e72461e5bd6c45aba2d8c641fc5dca33
Source dataset
uspto-grants-2016_08
Patent number
US09422324B2

Reaction notes

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