Hydrochloric Acid → 2,3-Difluoro-6-(1-methylenepropyl)anisole

HRID 1362501

Reaction equation

HRID 1362501 reaction equation
[Pb](Cl)Cl.Br[CH2:5]Br.[F:7][C:8]1[C:9]([O:19][CH3:20])=[C:10]([C:15](=O)[CH2:16][CH3:17])[CH:11]=[CH:12][C:13]=1[F:14].Cl>C1COCC1.ClCCl.C(OCC)C.[Zn].[Ti](Cl)(Cl)(Cl)Cl>[F:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([C:15](=[CH2:5])[CH2:16][CH3:17])[C:9]=1[O:19][CH3:20]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 3024DibromomethaneHCID 24459Lead chlorideHCID 669694841-(3,4-Difluoro-2-methoxyphenyl)propan-1-one

Product 1

HCID 669689902,3-Difluoro-6-(1-methylenepropyl)anisoleYield 40.9%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

31.2 g (476 mmol) of zinc dust and 740 mg (2.65 mmol) of lead(II) chloride are suspended in 320 ml of THF and at 0° C. 30 ml (265 mmol) of dibromomethane are added. The mixture is stirred at room temperature for a further 30 minutes and at 0° C. 53 ml (53 mmol) of a 1 M titanium(IV) chloride solution in dichloromethane are added dropwise. The cooling bath is removed and, after an hour, the reaction mixture is cooled to 0° C. again. 10.6 g (53 mmol) of 1-(3,4-difluoro-2-methoxyphenyl)propan-1-one in 106 ml of THF are added dropwise. The reaction mixture is stirred at room temperature for a further hour. It is diluted with diethyl ether and poured cautiously onto a mixture of 4 M hydrochloric acid and ice. The phases are separated, extracted is carried out with diethyl ether, the extracts are washed with saturated sodium chloride solution and dried over sodium sulphate and the solvent is removed. The crude product is purified by column chromatography on silica gel (hexane/diisopropyl ether 20-40%) to give 4.3 g of 2,3-difluoro-6-(1-methylenepropyl)anisole.

Workup

  1. customThe cooling bath is removed and, after an hour
  2. temperaturethe reaction mixture is cooled to 0° C. again
  3. stirringThe reaction mixture is stirred at room temperature for a further hour
  4. customThe phases are separated
  5. extractionextracted
  6. washthe extracts are washed with saturated sodium chloride solution
  7. dry with materialdried over sodium sulphate
  8. customthe solvent is removed
  9. customThe crude product is purified by column chromatography on silica gel (hexane/diisopropyl ether 20-40%)

Sources & evidence

ORD record
ord-d6b33fd374c74b57b2a9d03d57fa5120
Source dataset
uspto-grants-2011_02
Patent number
US07880042B2

Linked notes

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