Triethyl phosphonoacetate → (E)-(R)-4-tert-butoxycarbonylamino-6-(4-heptyloxy-phenyl)-4-methyl-hex-2-enoic acid ethyl ester

Temperature

-78 °C

To a stirred solution of (diethoxy-phosphoryl)-acetic acid ethyl ester (429 mg, 1.92 mMol) in dry THF (7 ml) is added n-butyllithium (0.66 ml, 2.5M in hexane, 1.66 mMol) at −78° C. The mixture was stirred at −78° C. for 1 hour. After that time, a solution of [(R)-1-formyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester (500 mg, 1.28 mMol) in THF (4 ml) is added and stirring is continued at −78° C. for 1.5 hours. The mixture is allowed to warm to RT and then stirred at RT for 2 hours. The reaction mixture is then poured onto a biphasic mixture of AcOEt and NaHCO3 (saturated aqueous solution) and the aqueous phase is extracted twice with AcOEt. The combined organic layers are dried (Na2SO4) and concentrated under reduced pressure. Column chromatography eluting with 4% AcOEt in toluene gives the title compound as a colourless oil.

1. stirringstirring
2. waitis continued at −78° C. for 1.5 hours
3. temperatureto warm to RT
4. stirringstirred at RT for 2 hours
5. extractionthe aqueous phase is extracted twice with AcOEt
6. dry with materialThe combined organic layers are dried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. washColumn chromatography eluting with 4% AcOEt in toluene

ORD record

ord-e219271ff5654914b84b2a1a70a9aa35

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07728020B2