Lithium diisopropylamide → 2-But-3-enyloxy-3-{3,5-dimethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-3-hydroxy-propionic acid ethyl ester

To a stirred 2 M solution of LDA in THF (0.38 ml, 0.76 mmol) was added a cooled (−78° C.) solution of but-3-enyloxy-acetic acid ethyl ester (120 mg, 0.76 mmol) in THF (3 ml) at −78° C. (for the preparation of but-3-enyloxy-acetic acid ethyl ester see: A. F. Noels, A. Demonceau, N. Petiniot, A. J. Hubert, P. Teyssié, Tetrahedron 1982, 38, 2733-2739). The solution was stirred for 10 min and then a solution of 3,5-dimethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzaldehyde (254 mg, 0.76 mmol, example 117) in THF (3 ml) was added. The reaction mixture was stirred 30 min at −78° C. and then quenched by the addition of sat. NH4Cl at −78° C. The solution was diluted with water and ethyl acetate, the layers were separated and the aqueous phase was extracted two times with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. Evaporation of the solvent gave a yellow oil which was purified by column chromatography (silica gel, hexane/AcOEt=9/1) to give 160 mg (0.32 mmol, 43%) of the title compound as a mixture of diastereomers as colorless oil.

1. stirringThe reaction mixture was stirred 30 min at −78° C.
2. customquenched by the addition of sat. NH4Cl at −78° C
3. additionThe solution was diluted with water and ethyl acetate
4. customthe layers were separated
5. extractionthe aqueous phase was extracted two times with ethyl acetate
6. washThe combined organic layers were washed with brine
7. dry with materialdried over sodium sulfate
8. customEvaporation of the solvent
9. customgave a yellow oil which
10. customwas purified by column chromatography (silica gel, hexane/AcOEt=9/1)

ORD record

ord-b13d7243f57248ac8c201b41ae577752

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06642389B2