Ethyl Acetate → 5-{4-[1-ethyl-1-(4-hydroxy-3-methyl-phenyl)-propyl]-2-methyl-phenyl}-4-methyl-thiophene-2-carboxylic Acid Methyl Ester

HRID 546838

Reaction equation

Br[C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][C:3]=1[CH3:11].C(=O)([O-])[O-].[Na+].[Na+].[CH2:18]([C:20]([C:39]1[CH:44]=[CH:43][C:42]([OH:45])=[C:41]([CH3:46])[CH:40]=1)([C:23]1[CH:28]=[CH:27][C:26](B2OC(C)(C)C(C)(C)O2)=[C:25]([CH3:38])[CH:24]=1)[CH2:21][CH3:22])[CH3:19].C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH3:10][O:9][C:7]([C:5]1[S:6][C:2]([C:26]2[CH:27]=[CH:28][C:23]([C:20]([CH2:21][CH3:22])([C:39]3[CH:44]=[CH:43][C:42]([OH:45])=[C:41]([CH3:46])[CH:40]=3)[CH2:18][CH3:19])=[CH:24][C:25]=2[CH3:38])=[C:3]([CH3:11])[CH:4]=1)=[O:8]

Participants

Conditions

Temperature: 85 °C

Procedure

Methyl 5-bromo-4-methyl-2-thiophenecarboxylate (178.85 mg, 0.761 mmol), tetrakistriphenylphosphine palladium (14.7 mg, 0.013 mmol) and a 2 M sodium carbonate aqueous solution (0.3 mL, 0.6 mmol) were added to a solution of 4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenol (Example 15-(2); 100 mg, 0.254 mmol) in toluene (0.5 mL) at room temperature, and the mixture was stirred at 85° C. for 17 hours. Ethyl acetate was added to the reaction solution. The organic layer was filtered through celite, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/ethyl acetate=3/1) to give the title compound (50.3 mg, 46.9%).

Workup

filtrationThe organic layer was filtered through celite
distillationthe solvent was distilled off under reduced pressure
customThe residue was purified by silica gel chromatography (n-hexane/ethyl acetate=3/1)

Sources & evidence

ORD record: ord-9c0370da1bdb425ba0d2a700dfd6e3fd
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07935688B2

Linked notes

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