4-Hydroxybenzaldehyde → 4-(Cyclobutylmethoxy)benzaldehyde

HRID 1485057Notes

Reaction equation

HRID 1485057 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1.Br[CH2:13][CH:14]1[CH2:17][CH2:16][CH2:15]1.Cl>CN(C)C=O.C(OCC)(=O)C>[CH:14]1([CH2:13][O:3][C:4]2[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=2)[CH2:17][CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 2734658(Bromomethyl)cyclobutane

Product 1

HCID 654582914-(Cyclobutylmethoxy)benzaldehydeYield 76.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of sodium hydride (60% dispersion in mineral oil, 0.328 g) in N,N-dimethylformamide (15.0 mL), a solution of 4-hydroxybenzaldehyde (1.00 g) in N,N-dimethylformamide (5.00 mL) was added at 0° C. and thereafter the mixture was stirred at room temperature for 30 minutes. After adding (bromomethyl)cyclobutane (1.22 g), the mixture was stirred at 70° C. for 24 hours. After cooling the reaction mixture to room temperature, 0.5 mol/L hydrochloric acid was added under cooling with ice and three extractions were conducted with ethyl acetate. The combined organic layers were passed through a phase separator and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=95:5-40:60) to give the titled compound as a colorless oil (1.19 g).

Workup

  1. stirringthe mixture was stirred at 70° C. for 24 hours
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. temperatureunder cooling with ice and three extractions
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=95:5-40:60)

Sources & evidence

ORD record
ord-793f93a6b864458891ae36d53bd1b4f9
Source dataset
uspto-grants-2016_08
Patent number
US09422240B2

Reaction notes

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