Cesium carbonate → 3-(4-Bromo-3-fluoro-phenoxy)-5-methoxymethoxybenzoic acid methyl ester

HRID 2354994Notes

Reaction equation

HRID 2354994 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[F:9].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:16][O:17][C:18](=[O:30])[C:19]1[CH:24]=[C:23]([OH:25])[CH:22]=[C:21]([O:26][CH2:27][O:28][CH3:29])[CH:20]=1>N1C=CC=CC=1.[Cu]=O>[CH3:16][O:17][C:18](=[O:30])[C:19]1[CH:20]=[C:21]([O:26][CH2:27][O:28][CH3:29])[CH:22]=[C:23]([O:25][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([F:9])[CH:4]=2)[CH:24]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27250061-Bromo-2-fluoro-4-iodobenzeneHCID 23136427Methyl 3-hydroxy-5-(methoxymethoxy)benzoate

Product 1

HCID 687084713-(4-Bromo-3-fluoro-phenoxy)-5-methoxymethoxybenzoic acid methyl esterYield 65%

Reagents, catalysts & solvents 2

HCID 14829Copper oxideCatalystHCID 1049PyridineSolvent

Conditions

Temperature
130 °C

Procedure

After adding 20.4 g (0.68 mol) of 1-bromo-2-fluoro-4-iodobenzene, 20.8 g (0.64 mol) of cesium carbonate and 5.07 g (0.64 mol) of copper (II) oxide to a solution of 9.00 g (0.43 mol) of 5-hydroxy-3-methoxymethoxybenzoic acid methyl ester in pyridine (50.0 ml), the mixture was stirred at 130° C. for 8 hours under a nitrogen atmosphere. The reaction mixture was filtered and then concentrated under reduced pressure, acetic acid ethyl ester and saturated aqueous ammonium chloride were added to the obtained residue, and the organic layer was washed with brine, dried and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:acetic acid ethyl ester=9:1) to obtain 10.6 g of 3-(4-bromo-3-fluoro-phenoxy)-5-methoxymethoxybenzoic acid methyl ester (yield: 65%) as a yellow oil.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated under reduced pressure, acetic acid ethyl ester and saturated aqueous ammonium chloride
  3. additionwere added to the obtained residue
  4. washthe organic layer was washed with brine
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (hexane:acetic acid ethyl ester=9:1)

Sources & evidence

ORD record
ord-76e136b49dca4799bb8314ebf0d1548c
Source dataset
uspto-grants-2010_07
Patent number
US07754743B2

Reaction notes

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