Hydrochloric Acid → ethyl (4-bromo-2-formylphenoxy)acetate

HRID 1836952Notes

Reaction equation

HRID 1836952 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:10])=[C:6]([CH:9]=1)[CH:7]=[O:8].[H-].[Na+].Br[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].Cl>CN(C=O)C>[CH2:18]([O:17][C:15](=[O:16])[CH2:14][O:10][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:9][C:6]=1[CH:7]=[O:8])[CH3:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 728635-Bromosalicylaldehyde

Product 1

HCID 880259ethyl (4-bromo-2-formylphenoxy)acetateYield 98.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

This compound was prepared according to a literature procedure (Yoo et al., Bioorg. Med. Chem. 5:445, 1997). 5-Bromo-2-hydroxybenzaldehyde (10.0 g, 49.7 mmol) was dissolved in 90 mL anhyd. DMF and the mixture was cooled to 0° C. NaH (60% dispersion in mineral oil, 2.38 g, 59.6 mmol) was added in portions and the reaction was stirred at 0° C. for 1 hour. Ethyl bromoacetate (9.95 g, 59.6 mmol) was then added dropwise over 10 minutes and the reaction was stirred at rt overnight (18 hours). After this time, 30 mL of 1 N HCl was added to adjust the pH to acidity, and the reaction mixture was transferred to a separatory funnel and extracted with EtOAc (3×60 mL). The combined organics rinsed with water (2×40 mL), dried over MgSO4, filtered, and concentrated in vacuo to provide a thick oil. Purification by flash chromatography (10% EtOAc/hexanes) provided the product as a clear oil (14.0 g, 98%). 1H-NMR (CD2Cl2, δ): 1.29 (t, 3H), 4.26 (q, 2H), 4.78 (s, 2H), 6.83 (d, 1H), 7.65 (dd, 1H), 7.94 (s, 1H), 10.47 (s, 1H); LRMS (GC/MS/EI) 286 [M]+.

Workup

  1. customThis compound was prepared
  2. stirringthe reaction was stirred at rt overnight (18 hours)
  3. customthe reaction mixture was transferred to a separatory funnel
  4. extractionextracted with EtOAc (3×60 mL)
  5. washThe combined organics rinsed with water (2×40 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a thick oil
  10. customPurification by flash chromatography (10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f8820a3ebe2848f4aceb6fe95d67b2eb
Source dataset
uspto-grants-2004_08
Patent number
US06780859B2

Reaction notes

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