Hexane → 4-((3-((Tert-butyldimethylsilyl)oxy)phenyl)(hydroxy)methyl)-N,N-diethylbenzamide

HRID 2258319Notes

Reaction equation

HRID 2258319 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].C([Li])CCC.CCCCCC.[CH:27]([C:29]1[CH:41]=[CH:40][C:32]([C:33]([N:35]([CH2:38][CH3:39])[CH2:36][CH3:37])=[O:34])=[CH:31][CH:30]=1)=[O:28]>O1CCCC1.C(O)C.ClCCl>[Si:6]([O:5][C:4]1[CH:3]=[C:2]([CH:15]=[CH:14][CH:13]=1)[CH:27]([C:29]1[CH:41]=[CH:40][C:32]([C:33]([N:35]([CH2:36][CH3:37])[CH2:38][CH3:39])=[O:34])=[CH:31][CH:30]=1)[OH:28])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]

Participants

8

Reactant 4

HCID 8058HexaneHCID 10954698N,N-diethyl-4-formylbenzamideHCID 11254705(3-Bromophenoxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium

Product 1

HCID 223500144-((3-((Tert-butyldimethylsilyl)oxy)phenyl)(hydroxy)methyl)-N,N-diethylbenzamideYield 52.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

3-Bromophenoxy-tert-butyldimethylsilane (61.7 g, 0.21 mol), prepared as in Example 1, was dissolved in 500 mL of dry tetrahydrofuran under nitrogen and cooled to -78° C. A solution of 1.6M n-butyllithium in hexane (132 mL, 0.21 mol) was added dropwise at a rate to maintain the temperature below -70° C. The reaction was stirred for thirty minutes after the addition was complete and the cold solution was transferred via cannula to another vessel containing a cold (-78 ° C.) solution of 4-formyl-N,N-diethylbenzamide (44.1 g, 0.21 mol), from above, in 500 mL of dry tetrahydrofuran under nitrogen. The transfer rate was monitored to maintain the temperature below -70° C. After stirring for one hour at -78° C., the reaction was quenched with saturated aqueous ammonium chloride, warmed to room temperature and diluted with diethyl ether. The ethereal layer was washed with water and brine, dried over sodium sulfate and evaporated to give a yellow oil. Chromatography on silica gel with dichloromethane: ethanol (0-1%) gave 45.4 g (52%) of 4-(3-(tert-butyl dimethylsiiyloxy)-α-hydroxybenzyl)-N,N -diethylbenzamide as a white solid.

Workup

  1. temperatureto maintain the temperature below -70° C
  2. additionafter the addition
  3. customthe cold solution was transferred via cannula to another vessel
  4. temperatureto maintain the temperature below -70° C
  5. stirringAfter stirring for one hour at -78° C.
  6. customthe reaction was quenched with saturated aqueous ammonium chloride
  7. temperaturewarmed to room temperature
  8. additiondiluted with diethyl ether
  9. washThe ethereal layer was washed with water and brine
  10. dry with materialdried over sodium sulfate
  11. customevaporated
  12. customto give a yellow oil

Sources & evidence

ORD record
ord-78f64e71163347c18d7ed712ee21f4af
Source dataset
uspto-grants-1997_08
Patent number
US05658908

Reaction notes

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