tert-Butanol → (4S)-11-[2-(dimethyl-pyrrolidin-1-ylmethyl-silanyl)-ethyl]-4-ethyl-4-hydroxy-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione

HRID 2246547Notes

Reaction equation

HRID 2246547 reaction equation
I[CH2:2][Si:3]([CH3:33])([CH3:32])[CH2:4][CH2:5][C:6]1[C:18]2[CH2:17][N:16]3[C:11](=[CH:12][C:13]4[C@:23]([CH2:25][CH3:26])([OH:24])[C:22](=[O:27])[O:21][CH2:20][C:14]=4[C:15]3=[O:19])[C:10]=2[N:9]=[C:8]2[CH:28]=[CH:29][CH:30]=[CH:31][C:7]=12.C([O-])([O-])=O.[K+].[K+].CC(O)(C)C.[NH:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1>O>[CH3:32][Si:3]([CH3:33])([CH2:2][N:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1)[CH2:4][CH2:5][C:6]1[C:18]2[CH2:17][N:16]3[C:11](=[CH:12][C:13]4[C@:23]([CH2:25][CH3:26])([OH:24])[C:22](=[O:27])[O:21][CH2:20][C:14]=4[C:15]3=[O:19])[C:10]=2[N:9]=[C:8]2[CH:28]=[CH:29][CH:30]=[CH:31][C:7]=12

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 5765938311-(4S)-[2-(iodomethyldimethylsilanyl)-ethyl]-4-ethyl-4-hydroxy-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione

Product 1

HCID 25261405(4S)-11-[2-(dimethyl-pyrrolidin-1-ylmethyl-silanyl)-ethyl]-4-ethyl-4-hydroxy-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dioneYield 83%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A slurry of Compound 4 (60 mg) and K2CO3 (43 mg) in deionized water (1 mL) was stirred at room temperature for 30 min. To the resulting reaction mixture, t-BuOH (1 mL) and pyrrolidine (52 μL) were added and heated at 70° C. for 5 hours. The reaction mixture was then concentrated under reduced pressure and the residue was dissolved in acetic acid (10 mL) and stirred at room temperature for 2 hours. The acetic acid solution was concentrated again under vacuum. Finally, the residue was partitioned between chloroform (2×15 mL) and 7% aqueous NaHCO3 solution (5 mL). The collective organic layers were dried, concentrated and purified on a silica gel using 10% ethanol in dichloromethane to afford the required product in 83% yield (45 mg).

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was then concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in acetic acid (10 mL)
  4. concentrationThe acetic acid solution was concentrated again under vacuum
  5. customFinally, the residue was partitioned between chloroform (2×15 mL) and 7% aqueous NaHCO3 solution (5 mL)
  6. customThe collective organic layers were dried
  7. concentrationconcentrated
  8. custompurified on a silica gel using 10% ethanol in dichloromethane

Sources & evidence

ORD record
ord-07e16c087021415fb1cc02c7c87562a0
Source dataset
uspto-grants-2010_03
Patent number
US07687496B2

Reaction notes

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