3-(t-Butyldimethylsiloxy)iodobenzene → 4-((3-((Tert-butyldimethylsilyl)oxy)phenyl)(hydroxy)methyl)-N,N-diethylbenzamide

HRID 2249466Notes

Reaction equation

HRID 2249466 reaction equation
I[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([Mg]Cl)(C)C.[CH:21]([C:23]1[CH:35]=[CH:34][C:26]([C:27]([N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[O:28])=[CH:25][CH:24]=1)=[O:22]>O1CCCC1>[Si:6]([O:5][C:4]1[CH:3]=[C:2]([CH:21]([OH:22])[C:23]2[CH:24]=[CH:25][C:26]([C:27]([N:29]([CH2:30][CH3:31])[CH2:32][CH3:33])=[O:28])=[CH:34][CH:35]=2)[CH:15]=[CH:14][CH:13]=1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 27572803-(t-Butyldimethylsiloxy)iodobenzeneHCID 10954698N,N-diethyl-4-formylbenzamideHCID 178418918HCID 178418918, compound

Product 1

HCID 223500144-((3-((Tert-butyldimethylsilyl)oxy)phenyl)(hydroxy)methyl)-N,N-diethylbenzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-Iodophenoxy-tert-butyldimethylsilane (48.85 g, 146 mmol) was placed in a 250 mL flask with 180 mL of dry tetrahydrofuran at room temperature under nitrogen, Isopropylmagnesium chloride (73 mL, 146 mmol, 2.0 M solution in tetrahydrofuran) was added through an addition funnel to form a light yellow solution. The reaction was stirred at room temperature for 1 hour. In the meantime, 30 g of 4-formyl-N,N-diethylbenzamide was dissolved in 300 mL of dry tetrahydrofuran in another 1000 mL flask and cooled to −72° C. under nitrogen. The freshly prepared 3-phenoxy-tert-butyl-dimethylsilane magnesium chloride was slowly added into the 1000 mL flask. The transfer rate was monitored to maintain reaction temperature below −70° C. The reaction was allowed to warm to room temperature while stirring overnight. The mixture was quenched with 24 mL of saturated aqueous ammonium chloride, diluted with 600 mL of diethyl ether, and washed with 600 mL of water followed by 150 mL of saturated sodium chloride. The ethereal solution was dried over sodium sulfate and the solvent was removed to give crude 4-{[3-(tert-butyl-dimethylsilanyloxy)phenyl]hydroxymethyl}-N,N-diethylbenzamide as a yellow oil. Crude yield was˜100%. The crude product was slurried in a solution of 20% ethyl acetate in pentane. The resulting white precipitate was collected by filtration, washed with pentane, and dried overnight (30 mmHg, 40° C.).

Workup

  1. customto form a light yellow solution
  2. temperaturecooled to −72° C. under nitrogen
  3. temperatureto maintain
  4. customreaction temperature below −70° C
  5. temperatureto warm to room temperature
  6. stirringwhile stirring overnight
  7. customThe mixture was quenched with 24 mL of saturated aqueous ammonium chloride
  8. additiondiluted with 600 mL of diethyl ether
  9. washwashed with 600 mL of water
  10. dry with materialThe ethereal solution was dried over sodium sulfate
  11. customthe solvent was removed

Sources & evidence

ORD record
ord-770affecdcfc4bdfae2e2c354bd40acf
Source dataset
uspto-grants-2008_01
Patent number
US07314880B2

Reaction notes

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