Triethylamine → Methyl 3-(2-bromo-3,5-difluorophenyl)propanoate

HRID 625696Notes

Reaction equation

HRID 625696 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[Br:10].[CH3:11][O:12][CH:13]([O:16]C)[CH:14]=[CH2:15].C(N(CC)CC)C>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[Br:10][C:3]1[C:4]([F:9])=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[CH2:15][CH2:14][C:13]([O:12][CH3:11])=[O:16]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 80145Acrolein dimethyl acetalHCID 27245171,2-Dibromo-3,5-difluorobenzene

Product 1

HCID 89826041Methyl 3-(2-bromo-3,5-difluorophenyl)propanoate

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1,2-dibromo-3,5-difluorobenzene (4.5 g), 3,3-dimethoxyprop-1-ene (5.1 mL), tetrabutylammonium chloride (4.6 g) and triethylamine (3.5 mL) in N,N-dimethylformamide (50 mL) is purged with nitrogen for 20 minutes. Palladium-(II)-acetate (111 mg) is added and the mixture heated for 16 hours at 90° C. After cooling the mixture is partitioned between aqueous HCl (1 M) and diethyl ether, the organic layer dried (Na2SO4), volatiles evaporated under reduced pressure and the residue purified by column chromatography (silica gel; hexane:ethyl acetate 98:2→80:20) to give the title compound (Yield 3.6 g).

Workup

  1. customis purged with nitrogen for 20 minutes
  2. additionPalladium-(II)-acetate (111 mg) is added
  3. temperatureAfter cooling the mixture
  4. customis partitioned between aqueous HCl (1 M) and diethyl ether
  5. dry with materialthe organic layer dried (Na2SO4)
  6. customvolatiles evaporated under reduced pressure
  7. customthe residue purified by column chromatography (silica gel; hexane:ethyl acetate 98:2→80:20)

Sources & evidence

ORD record
ord-8f53b8bc5e954936a05f94d1a5e40149
Source dataset
uspto-grants-2016_04
Patent number
US09308194B2

Reaction notes

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