Ethyl orthoformate → 2-Bromo-4-(diethoxymethyl)-1-fluorobenzene

HRID 1961545Notes

Reaction equation

HRID 1961545 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])C=O.[CH:11]([O:18][CH2:19][CH3:20])([O:15][CH2:16][CH3:17])OCC.[Br-].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(O)=O.[Na+]>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:11]([O:15][CH2:16][CH3:17])[O:18][CH2:19][CH3:20])[CH:7]=[CH:8][C:9]=1[F:10]

Participants

6

Reactant 4

HCID 31214Ethyl orthoformateHCID 1736043-Bromo-4-fluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 23500184Tetra-n-butylammonium tribromide

Product 1

HCID 131165852-Bromo-4-(diethoxymethyl)-1-fluorobenzeneYield 74%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 10 mL vial equipped with stir bar was charged with 1 g of 3-bromo-4-fluoro-benzaldehyde, 2 mL of triethyl orthoformate, and 5 mL of anhydrous ethanol. 50 mgs of tetrabutylammonium tribromide was then added, and the reaction mixture was stirred at ambient temperature overnight. TLC shows complete conversion to slightly less polar product. The crude reaction is poured into NaHCO3, and extracted with ethyl acetate (2×25 mL). Combined organics are dried over MgSO4, and filtered over a pad of silica. The solvents are reduced under vacuum and a colorless oil (1 g) is isolated. The diethyl acetal intermediate is used as such in the next step. 74% yield.

Workup

  1. customA 10 mL vial equipped
  2. stirringthe reaction mixture was stirred at ambient temperature overnight
  3. customThe crude reaction
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. dry with materialCombined organics are dried over MgSO4
  6. filtrationfiltered over a pad of silica

Sources & evidence

ORD record
ord-013c0ceea38b46ebb4121fc655bdeda2
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

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