Ethyl oxoacetate → 2-Hydroxy-3-methyl-4-oxo-4-(2-phenyl-thiazol-5-yl)-butyric Acid Ethyl Ester

Temperatur

-20 °C

To a −78° C. solution of 0.26 g (1.2 mmol) of the above-prepared 1-(2-phenyl-thiazol-5-yl)-propan-1-one was added 0.24 g (1.4 mmol) of 1M lithium bis(trimethylsilyl)amide in tetrahydrofuran. The mixture was allowed to stir for 0.5 hours and then 0.38 g (1.5 mmol) of 1M chlorotitanium triisopropoxide in hexanes was added. The reaction was allowed to warm to −20° C. and stirred for 15 minutes. The reaction was recooled to. −78° C. and 0.25 g (0.24 mmol) of ethyl glyoxalate in toluene(50%) was added. The solution was warmed to room temperature and allowed to stir for 0.5 hours. The reaction was quenched with aqueous potassium sodium tartrate tetrahydrate and partitioned with ethyl acetate. The organic phase was twice washed with aqueous potassium sodium tartrate tetrahydrate, once with water, once with brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by chromatography on silica gel using 1:9 ethyl acetate:hexanes to give 0.15 g of the title compound (40%). 1H NMR (500 MHz, CDCl3) δ 8.42 (s, 1H) 8.01 (d, 2H) 7.48 (m, 3H) 5.8 (m, 1H) 4.27 (q, 2H) 3.75 (m, 1H) 3.28 (m, 1H) 1.37 (d, 3H) 1.26 (t, 3H).

1. stirringstirred for 15 minutes
2. temperatureThe solution was warmed to room temperature
3. stirringto stir for 0.5 hours
4. customThe reaction was quenched with aqueous potassium sodium tartrate tetrahydrate
5. custompartitioned with ethyl acetate
6. washThe organic phase was twice washed with aqueous potassium sodium tartrate tetrahydrate, once with water, once with brine
7. dry with materialdried over sodium sulfate
8. customThe solvent was evaporated under reduced pressure
9. customthe residue was purified by chromatography on silica gel using 1:9 ethyl acetate

ORD-Eintrag

ord-597858f11029412d96b31c6bd8ad78c2

Quelldatensatz

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06608087B1