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

HRID 1969188Notes

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].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

Conditions

Temperature: 105 °C

Procedure

(2-Methyl-4-mercapto-phenoxy)-acetic acid ethyl ester (6 g; 26.51 mmol), dibromophenol (8.68 g; 34.47 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.97 g; 1.06 mmol), and 1,1′-bis-(diphenylphosphineo)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

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

Sources & evidence

ORD record: ord-60068e2f3c824767970187c738aed0eb
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426473B2

Reaction notes

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