Reacción #330834

Ecuación de reacción

lithium chloride

(4S)-4-phenyl-1,3-oxazolidin-2-one

5-hexynoic acid

triethylamine

trimethylacetyl chloride

→

title compound

Rendimiento 85.4%

(4S)-3-Hex-5-ynoyl-4-phenyl-1,3-oxazolidin-2-one

Rendimiento 85.4%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONUpon addition a white precipitate
2. 2
   Otroformed
3. 3
   OtroAll volatiles were removed in vacuo
4. 4
   workup.ADDITIONthe residue was diluted with water (1 L)
5. 5
   Extracciónextracted with ethyl acetate (3×300 mL)
6. 6
   LavadoThe combined organic layers were washed with brine (250 mL)
7. 7
   Secadodried over magnesium sulfate
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated in vacuo
10. 10
    OtroThe crude residue was purified by silica gel chromatography
11. 11
    Lavadoeluting with a 5-50% ethyl acetate in hexanes gradient

Procedimiento

To a solution of 69.0 g (615 mmol) of 5-hexynoic acid and 214 mL (1540 mmol) of triethylamine in 1.0 L of anhydrous tetrahydrofuran at −25° C. under an atmosphere of nitrogen was added 83.0 mL (677 mmol) of trimethylacetyl chloride over 20 min. Upon addition a white precipitate formed and the resulting suspension was stirred for 2 h. Next, 28.7 g (677 mmol) of anhydrous lithium chloride and 100.0 g (615.0 mmol) of (4S)-4-phenyl-1,3-oxazolidin-2-one were added sequentially and the mixture was allowed to gradually warm to ambient temperature over 12 h. All volatiles were removed in vacuo and the residue was diluted with water (1 L) and extracted with ethyl acetate (3×300 mL). The combined organic layers were washed with brine (250 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography eluting with a 5-50% ethyl acetate in hexanes gradient to afford the title compound as a colorless solid (135 g, 85.4%). 1H NMR (500 MHz, CDCl3): δ 7.40-7.37 (m, 2H), 7.36-7.32 (m, 1H), 7.31-7.28 (m, 2H), 5.42 (dd, J=8.9, 3.7 Hz, 1H), 4.69 (t, J=8.9 Hz, 1H), 4.28 (dd, J=9.2, 3.7 Hz, 1H), 3.13-3.02 (m, 2H), 2.24-2.21 (m, 2H), 1.94 (t, J=2.6 Hz, 1H), 1.84 (quintet, J=7.1 Hz, 2H). LC-MS: m/z (ES) 258.2 (MH)+.

Fuente