Sodium hydride → 2-Chloro-4-(4-chloro-2-fluoro-benzyloxy)-5-methoxy-benzaldehyde

HRID 253458

Reaction equation

HRID 253458 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([OH:10])[C:7]([O:11][CH3:12])=[CH:6][C:3]=1[CH:4]=[O:5].[H-].[Na+].Br[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[F:24]>CN(C)C=O>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[F:24])[C:7]([O:11][CH3:12])=[CH:6][C:3]=1[CH:4]=[O:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 290002-Chloro-4-hydroxy-5-methoxybenzaldehydeHCID 27365514-Chloro-2-fluorobenzyl bromide

Product 1

HCID 598038352-Chloro-4-(4-chloro-2-fluoro-benzyloxy)-5-methoxy-benzaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Chloro-4-hydroxy-5-methoxy-benzaldehyde (136, 0.548 g, 2.94 mmol, prepared as described in Example 46, Scheme 45, step 1) was dissolved in N,N-dimethylformamide (40 mL) and sodium hydride (60% dispersion in mineral oil, 0.200 g, 5.00 mmol) was added. After 20 minutes, 1-bromomethyl-4-chloro-2-fluoro-benzene (139, 685 μL, 5.00 mmol) was added to the reaction mixture. The reaction was stirred at room temperature under an atmosphere of nitrogen for 5.5 hours. The reaction was concentrated to dryness in vacuo. The reaction was resuspended in water/saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography, eluting with 5-35% ethyl acetate in hexane give a white solid (140, 0.942 g, 97%), consistent with the desired compound by 1H-NMR.

Workup

  1. concentrationThe reaction was concentrated to dryness in vacuo
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. custompurified by silica gel column chromatography
  7. washeluting with 5-35% ethyl acetate in hexane
  8. customgive a white solid (140, 0.942 g, 97%)

Sources & evidence

ORD record
ord-b926d63280ac4b59b2ebad044c849da3
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Linked notes

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