Dimethylformamide → 2-Fluoro-4-methoxybenzaldehyde

HRID 2212587Notes

Reaction equation

HRID 2212587 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[F:10].[Li]CCCC.CN([CH:19]=[O:20])C.[NH4+].[Cl-]>C1COCC1>[F:10][C:3]1[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=1[CH:19]=[O:20]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 37184441-Bromo-2-fluoro-4-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 27348732-Fluoro-4-methoxybenzaldehydeYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-bromo-3-fluoro anisole (34.4 g, 168 mmol) in anhydrous THF (300 mL) was added dropwise, at −78° C. under argon, n-BuLi (2.5 M in THF, 101 mL, 252 mol). After 5 min DMF (40 mL, 503 mmol) was added and the reaction micture was kept at −78° C. for 2 hrs. Aqueous NH4Cl (250 mL) was carefully added and the layers separated. The aqueous phase was further extracted with ethyl acetate. The organic phases were combined and washed successively with water, brine and dried (MgSO4). The residue was purified on silica gel (eluent: 10% ethyl acetate in hexane) to give 13.99 g of 2-fluoro-4-methoxy-benzaldehyde (54%). 1H NMR (300 MHz; CDCl3): 3.88 (s, 3 H), 6.65 (d, J=12.3 Hz, 1 H), 6.80 (d, J=8.7 Hz, 1 H), 7.82 (t, J=8.7 Hz, 1 H), 10.21 (s, 1 H).

Workup

  1. customthe layers separated
  2. extractionThe aqueous phase was further extracted with ethyl acetate
  3. washwashed successively with water, brine
  4. dry with materialdried (MgSO4)
  5. customThe residue was purified on silica gel (eluent: 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8ce339961f08454d81ff1403fac64724
Source dataset
uspto-grants-2006_09
Patent number
US07102000B2

Reaction notes

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