Hydrochloric Acid → HCID 21220442, compound

HRID 1584814Notes

Reaction equation

HRID 1584814 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([F:12])[C:3]=1[CH2:13][OH:14].C(N(CC)CC)C.[C:22](OC(=O)C)(=[O:24])[CH3:23].Cl>C(Cl)Cl.O>[C:22]([O:14][CH2:13][C:3]1[C:4]([F:12])=[C:5]([CH:9]=[C:10]([F:11])[C:2]=1[Br:1])[C:6]([OH:8])=[O:7])(=[O:24])[CH3:23]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 21220332HCID 21220332, compound

Product 1

HCID 21220442HCID 21220442, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

In 18 ml of methylene chloride was suspended 1.80 g of 4-bromo-2,5-difluoro-3-hydroxymethylbenzoic acid and to the suspension were added 1.64 g of triethylamine and 0.84 g of acetic anhydride with ice-cooling, after which the suspension was stirred for one hour. The temperature of the suspension was then elevated to room temperature, at which the mixture was stirred for a further 12 hours. The reaction mixture was added to a mixed solvent of 20 ml of methylene chloride and 50 ml of water and the pH was adjusted to 1 with 6N hydrochloric acid. Thereafter, the organic layer formed was separated, washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue obtained was purified by a column chromatography (eluent: chloroform:ethanol=9:1), to obtain a colorless, oily 3-acetoxymethyl-4-bromo-2,5-difluorobenzoic acid. The oily product obtained was dissolved in 42 ml of anhydrous tetrahydrofuran, and 1.64 g of N,N'-carbonyldiimidazole was added to the solution with ice-cooling. The resulting mixture was stirred at room temperature for one hour. Subsequently, 1.45 g of magnesium ethoxycarbonylacetate was added thereto and the resulting mixture was stirred at the same temperature for 20 hours. The reaction mixture was added to a mixed solvent of 80 ml of ethyl acetate and 100 ml of water, and the pH was adjusted to 1 with 6N hydrochloric acid. Thereafter, the organic layer formed was separated, washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by a column chromatography (eluent: n-hexane:ethyl acetate=20:1), to obtain 1.32 g of colorless, crystalline ethyl 3-acetoxymethyl-4-bromo-2,5-difluorobenzoylacetate.

Workup

  1. temperaturecooling
  2. customwas then elevated to room temperature, at which
  3. stirringwas stirred for a further 12 hours
  4. customThereafter, the organic layer formed
  5. customwas separated
  6. washwashed with a saturated saline solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was removed by distillation under reduced pressure
  9. customThe residue obtained
  10. customwas purified by a column chromatography (eluent: chloroform:ethanol=9:1)

Sources & evidence

ORD record
ord-d5b92ad27d634f808d8befe03353cae7
Source dataset
uspto-grants-1999_08
Patent number
US05935952

Reaction notes

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