Dimethylformamide → 4-Chloro-2-fluoro-3-methoxybenzaldehyde

HRID 1988544Notes

Reaction equation

HRID 1988544 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([O:9][CH3:10])[C:3]=1[F:11].C([Li])CCC.CN([CH:20]=[O:21])C>C(OCC)C>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([CH:20]=[O:21])=[C:3]([F:11])[C:4]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 666003671-Bromo-4-chloro-2-fluoro-3-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 579319864-Chloro-2-fluoro-3-methoxybenzaldehydeYield 61%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

1-Bromo-4-chloro-2-fluoro-3-methoxybenzene (23.7 g, 99 mmol, see U.S. Pat. No. 7,300,907 for preparation) was dissolved in dry diethyl ether and cooled to −78° C. 2.5M n-Butyllithium in hexanes (44 mL, 110 mmol) was added in portions, keeping the temperature below −70° C. during the addition. DMF (15.5 mL, 200 mmol) was then added in portions, keeping the temperature below −60° C. The reaction mixture was then allowed to warm to ambient temperature and quenched with water. The organic phase was dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound in sufficient purity for subsequent reactions (11.4 g, 61% yield): 1H NMR (CDCl3) δ 10.32 (s, 1H), 7.55 (m, 1H), 7.3 (m, 1H), 4.05 (d, 3H).

Workup

  1. custom7,300,907 for preparation)
  2. customthe temperature below −70° C.
  3. additionduring the addition
  4. customthe temperature below −60° C
  5. temperatureto warm to ambient temperature
  6. customquenched with water
  7. customThe organic phase was dried
  8. concentrationconcentrated
  9. customThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-10d546a5d4f141d38f32600a91552fed
Source dataset
uspto-grants-2010_01
Patent number
US07642220B2

Reaction notes

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