Potassium Phosphate, Tribasic → (R)-[4'-(1-{4-[3-(t-butyl-dimethyl-silanyloxy)-4,4-dimethyl-pentyl]-3-methyl-phenyl}-1-ethyl-propyl)-2'-methyl-biphenyl-3-yl]-hydroxy-acetic Acid Methyl Ester

Degassed tetrahydrofuran (0.14 mL) was added to t-butyl-(1-{2-[4-(1-ethyl-1-{4-[4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl]-3-methyl-phenyl}-propyl)-2-methyl-phenyl]-ethyl}-2,2-dimethyl-propoxy)dimethylsilane (Example 24-(1); 14.4 mg, 0.0237 mmol), palladium (II) acetate (1.2 mg, 0.0053 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (4.5 mg, 0.011 mmol) and potassium phosphate (13.0 mg, 0.0612 mmol). The mixture was stirred in a nitrogen atmosphere for three minutes, followed by addition of (R)-(3-chloro-phenyl)-hydroxy-acetic acid methyl ester (Example 156-(1); 0.006 mL, 6.5 mg, 0.032 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 60 to 70° C. for four hours. The reaction mixture was diluted with diethyl ether and filtered through cotton plug, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=7/1) to give the title compound (3.6 mg, 24%).

1. customDegassed tetrahydrofuran (0.14 mL)
2. temperatureAfter replacement with nitrogen, the mixture was heated
3. stirringwhile stirring at an external temperature of 60 to 70° C. for four hours
4. filtrationfiltered through cotton plug
5. concentrationthe filtrate was concentrated under reduced pressure
6. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate=7/1)

ORD-Eintrag

ord-18ff8872d5004908b15a4d7f4b470a8a

Quelldatensatz

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07935688B2