Ethyl Acetate → 3-Bromo-2,5-difluorobenzaldehyde

HRID 577290

Reaction equation

HRID 577290 reaction equation
N[C:2]1[C:9]([F:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([F:11])[C:3]=1[Br:12].N([O-])=O.[Na+].C(OCC)(=O)C>C(O)(=O)C.P(P(O)(O)=O)(O)(O)=O.O>[Br:12][C:3]1[C:4]([F:11])=[C:5]([CH:8]=[C:9]([F:10])[CH:2]=1)[CH:6]=[O:7]

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 146210204-Amino-3-bromo-2,5-difluorobenzaldehydeHCID 23668193Sodium Nitrite

Product 1

HCID 146210213-Bromo-2,5-difluorobenzaldehydeYield 44.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 24536Hypophosphoric acidSolvent

Procedure

4-amino-3-bromo-2,5-difluorobenzaldehyde (3.4 g, 14.3 mmol) was dissolved in acetic acid (18 mL) before addition of hypophosphoric acid (50% in water, 39 mL). A solution of sodium nitrite (1.4 eq, 1.4 g) in water (8 mL) was then added dropwise under ice-cooling. After stirring at rt for 2 h, the reaction mixture was poured onto a mixture ice/water and the aqueous phase extracted with DCM. The combined organic phases were dried over sodium sulfate and evaporated. A column chromatography (0 to 10% ethyl acetate in petroleum ether) afforded 3-bromo-2,5-difluorobenzaldehyde (1.3 g, 6.3 mmol, 44%). 1H NMR (d6-DMSO) δ 10.15-10.12 (m, 1H), 8.13 (ddd, J=8.0, 5.0, 3.0 Hz, 1H), 7.66 (ddd, J=8.0, 5.0, 3.0 Hz, 1H).

Workup

  1. temperaturecooling
  2. extractionthe aqueous phase extracted with DCM
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. customevaporated

Sources & evidence

ORD record
ord-19461ba0a88e47f6977b84a25878986e
Source dataset
uspto-grants-2015_05
Patent number
US09040545B2

Linked notes

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