2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → Tert-butyl benzoate

Temperature

105 °C

4-Ethoxy-1-ethyl-1H-indole-2-carboxylic acid [4-((S)-pyrrolidin-3-yloxy)-phenyl]-amide hydrochloride (103 mg, 0.24 mmol) was mixed with 4-bromo-benzoic acid tert-butyl ester (74 mg, 0.29 mmol) in dioxane (4 mL). To this solution was added tris(dibenzylideneacetone)dipalladium (Pd2(dba)3, 20 mg), (2′,4′,6′-triisopropyl-1,1′-biphenyl-2-yl)dicyclohexylphosphine (X-PHOS, 35 mg) and sodium tert-butoxide (70 mg, 0.72 mmol). The mixture was degassed with argon and then sealed. The stirred solution was heated at 105° C. for 2 hrs and solvents were evaporated. The residue was extracted with ethyl acetate and ammonium chloride solution. The organic layer was dried over sodium sulfate and then concentrated. The residue was purified through flash column chromatography using ethyl acetate in hexanes (5% to 60%) to give a white solid as 4-(S)-3-{4-[(4-ethoxy-1-ethyl-1H-indole-2-carbonyl)-amino]-phenoxy}-pyrrolidin-1-yl)-benzoic acid tert-butyl ester (100 mg).

1. customThe mixture was degassed with argon
2. customsealed
3. customsolvents were evaporated
4. extractionThe residue was extracted with ethyl acetate and ammonium chloride solution
5. dry with materialThe organic layer was dried over sodium sulfate
6. concentrationconcentrated
7. customThe residue was purified through flash column chromatography

ORD record

ord-24acc8076209468988f06c07c18cf7c2

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08124766B2