Citric Acid → [4-(3-Bromo-5-hydroxy-phenylsulfanyl)-2-methyl-phenoxy]-acetic Acid Ethyl Acetate

HRID 549544Notes

Reaction equation

HRID 549544 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([SH:13])=[CH:9][C:8]=1[CH3:14])[CH3:2].[Br:16][C:17]1[C:18](Br)=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1.C(N(CC)CC)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].CN1C(=O)CCC1>[CH2:1]([O:3][C:4](=[O:15])[CH3:5])[CH3:2].[Br:16][C:17]1[CH:22]=[C:21]([S:13][C:10]2[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]([OH:3])=[O:15])=[C:8]([CH3:14])[CH:9]=2)[CH:20]=[C:19]([OH:23])[CH:18]=1

Participants

8

Reactant 4

HCID 311Citric AcidHCID 8471TriethylamineHCID 342642,3-DibromophenolHCID 16641178Ethyl (4-mercapto-2-methylphenoxy)acetate

Product 1

HCID 67024264[4-(3-Bromo-5-hydroxy-phenylsulfanyl)-2-methyl-phenoxy]-acetic Acid Ethyl Acetate

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
105 °C

Procedure

(2-Methyl-4-mercapto-phenoxy)-acetic acid ethyl ester (6 g; 26.51 mmol), dibromo-phenol (8.68 g; 34.47 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.97 g; 1.06 mmol), and 1,1′-bis-(diphenylphosphino)ferrocene (0.88 g; 1.59 mmol) were added to a dry reaction flask under an atmosphere of nitrogen. Triethylamine (10.73 mL, 106 mmol) and NMP (20 mL) were added, and the reaction mixture was stirred in a microwave oven for 1 h at 105° C. A 5% aqueous citric acid solution (150 mL) was added to the reaction mixture, which was extracted with ethyl acetate (4×100 mL). The pooled organic phases were washed twice with water (30 mL), dried and evaporated in vacuo. The crude reaction product was purified by flash chromatography (heptane:ethyl acetate (10:1→7:3). Yield 6.5 g. HPLC-MS: m/z: 397.3 (M+); Rt: 2.33 min.

Workup

  1. extractionwas extracted with ethyl acetate (4×100 mL)
  2. washThe pooled organic phases were washed twice with water (30 mL)
  3. customdried
  4. customevaporated in vacuo
  5. customThe crude reaction product
  6. customwas purified by flash chromatography (heptane:ethyl acetate (10:1→7:3)

Sources & evidence

ORD record
ord-88c5d72d599d473d9e7bcdb017c413e7
Source dataset
uspto-grants-2011_05
Patent number
US07943669B2

Reaction notes

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