Benzyl Alcohol → 4-(Benzyloxy)-2-chlorobenzaldehyde

HRID 475523Notes

Reaction equation

HRID 475523 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.F[C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[C:14]([Cl:20])[CH:13]=1>CN(C)C=O>[CH2:3]([O:10][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[C:14]([Cl:20])[CH:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 1450242-Chloro-4-fluorobenzaldehyde

Product 1

HCID 140340774-(Benzyloxy)-2-chlorobenzaldehydeYield 72.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (404.8 mg, 10.12 mmol, 60% dispersed oil) was slowly added to benzylalcohol (1 g, 9.2 mmol) dissolved in dried dimethylformamide (30 ml) under nitrogen at room temperature while stirring. Then, the mixture was further stirred at room temperature for 30 minutes. Thereto, 4-fluoro-2-chlorobenzaldehyde (1.46 g, 9.2 mmol) dissolved in dried dimethylformamide was added over 10 minutes and stirred at room temperature for 18 hours until the initial reaction product disappeared. Subsequently, ice water was added thereto, and the reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water several times, dried with anhydrous magnesium sulfate, filtered and solvent-evaporated. The residual oil was chromatographed on a silica gel column (hexane:ethyl acetate=20:1) to afford the intermediate, 4-(benzyloxy)-2-chlorobenzaldehyde (1.64 g, yield: 71.9%).

Workup

  1. stirringThen, the mixture was further stirred at room temperature for 30 minutes
  2. additionwas added over 10 minutes
  3. stirringstirred at room temperature for 18 hours until the initial
  4. customreaction product
  5. extractionthe reaction mixture was extracted with ethyl acetate and water
  6. washThe organic layer was washed with water several times
  7. dry with materialdried with anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customsolvent-evaporated
  10. customThe residual oil was chromatographed on a silica gel column (hexane:ethyl acetate=20:1)

Sources & evidence

ORD record
ord-147b8c3148a84054ad4ec9e94c32972f
Source dataset
uspto-grants-2014_01
Patent number
US08637558B2

Reaction notes

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