Citric Acid → [4-(3-Bromo-5-isobutoxy-phenylsulfanyl)-2,5-dimethyl-phenoxy]-acetic Acid Ethyl Ester

HRID 1969207Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH:10]([CH3:12])[CH3:11])[CH:5]=[C:4]([Br:13])[CH:3]=1.[CH2:14]([O:16][C:17](=[O:29])[CH2:18][O:19][C:20]1[CH:25]=[C:24]([CH3:26])[C:23]([SH:27])=[CH:22][C:21]=1[CH3:28])[CH3:15].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].CN1C(=O)CCC1>[CH2:14]([O:16][C:17](=[O:29])[CH2:18][O:19][C:20]1[CH:25]=[C:24]([CH3:26])[C:23]([S:27][C:2]2[CH:7]=[C:6]([O:8][CH2:9][CH:10]([CH3:12])[CH3:11])[CH:5]=[C:4]([Br:13])[CH:3]=2)=[CH:22][C:21]=1[CH3:28])[CH3:15]

Participants

Conditions

Temperature: 140 °C

Procedure

1,3-Dibromo-5-isobutoxy-benzene (1.66 g; 5.4 mmol), (4-Mercapto-2,5-dimethyl-phenoxy)-acetic acid ethyl ester (1.0 g; 4.1 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.11 g; 0.12 mmol), and 1,1′-bis-(diphenylphosphineo)ferrocene (0.14 g; 0.25 mmol) were added to a dry reaction flask under an atmosphere of nitrogen. Triethylamine (2.3 mL) and NMP (10 mL) was added, and the reaction mixture was stirred in a microwave oven for 1 h at 140° 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 dried and evaporated in vacuo. The crude reaction product was purified by flash chromatography (heptane: ethyl acetate (10:1→1:1). Yield: 1.3 g; 67%. HPLC-MS: m/z: 467.0 (M+); Rt: 3.10 min

Workup

extractionwas extracted with ethyl acetate (4×100 mL)
customThe pooled organic phases were dried
customevaporated in vacuo
customThe crude reaction product
customwas purified by flash chromatography (heptane: ethyl acetate (10:1→1:1)

Sources & evidence

ORD record: ord-cc2988fe5f6949759df609fe4acf6efe
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426473B2

Reaction notes

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