Hydrochloric Acid → 2-Chloro-3-fluoro-4-methoxybenzaldehyde

HRID 1191595Notes

Reaction equation

HRID 1191595 reaction equation
[Cl:1][C:2]1[C:3]([F:10])=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.CN([CH:19]=[O:20])C.Cl>C1COCC1.CCCCCC>[Cl:1][C:2]1[C:3]([F:10])=[C:4]([O:8][CH3:9])[CH:5]=[CH:6][C:7]=1[CH:19]=[O:20]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 27735843-Chloro-2-fluoroanisoleHCID 178418339Butyllithium

Product 1

HCID 538390722-Chloro-3-fluoro-4-methoxybenzaldehyde

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

1 g (6.2 mmol) 3-Chloro-2-fluoroanisole in 20 ml THF are cooled to −70° C. and 2.7 ml of a 2.5 M n-butyl lithium solution in hexane are added. After one hour at −70° 3.93 ml DMF in 7 ml THF are added at −70° C. and the mixture is stirred another hour at −70° C. 15 ml of a 1M aqueous HCl are added and the reaction is warmed to ambient temperature over 18 hours. The reaction mixture is partitioned between diethyl ether and water. The aqueous phase is extracted with diethyl ether, the combined organic phases are washed with brine, dried over sodium sulfate and evaporated. The crude product is purified by chromatography on silica gel to yield 0.25 g 2-chloro-3-fluoro-4-methoxybenzaldehyde. 1H-NMR (CDCl3); δ=3.98 (s, 3H), 6.98 (dd, 1H), 7.75 (dd, 1H), 10.30 (s, 1H).

Workup

  1. temperaturethe reaction is warmed to ambient temperature over 18 hours
  2. customThe reaction mixture is partitioned between diethyl ether and water
  3. extractionThe aqueous phase is extracted with diethyl ether
  4. washthe combined organic phases are washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe crude product is purified by chromatography on silica gel

Sources & evidence

ORD record
ord-559d3218ad3a4caeae80f5c35479f119
Source dataset
uspto-grants-2014_03
Patent number
US08680117B2

Reaction notes

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