Reacción #490629

Ecuación de reacción

lithium chloride

(S)-(−)-4-benzyl-2-oxazolidinone

5-hexynoic acid

triethylamine

trimethylacetyl chloride

→

title compound

Rendimiento 93.0%

(4S)-4-Benzyl-3-hex-5-ynoyl-1,3-oxazolidin-2-one

Rendimiento 93.0%

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 (500 mL)
5. 5
   Extracciónextracted with ether (3×200 mL)
6. 6
   LavadoThe combined organic layers were washed with brine (100 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 10-25% ethyl acetate in hexanes gradient

Procedimiento

To a solution of 10 g (89 mmol) of 5-hexynoic acid and 31.0 mL (223 mmol) of triethylamine in 450 mL of anhydrous tetrahydrofuran at −25° C. under an atmosphere of nitrogen was added 12 mL (98 mmol) of trimethylacetyl chloride over 20 min. Upon addition a white precipitate formed and the resulting suspension was stirred for 2 h. Next, 4.2 g (98 mmol) of anhydrous lithium chloride and 17 g (94 mmol) of (S)-(−)-4-benzyl-2-oxazolidinone 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 (500 mL) and extracted with ether (3×200 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography eluting with a 10-25% ethyl acetate in hexanes gradient to afford the title compound as a colorless solid (22 g, 93%). 1H NMR (500 MHz, CDCl3): δ 7.35-7.31 (m, 2H), 7.28-7.25 (m, 1H), 7.19-7.21 (m, 2H), 4.69-4.64 (m, 1H), 4.22-4.15 (m, 2H), 3.28 (dd, J=13.4, 3.3 Hz, 1H), 3.13-3.01 (m, 2H), 2.78 (dd, J=13.4, 9.6 Hz, 1H), 2.34-2.30 (m, 2H), 1.99 (t, J=2.7 Hz, 1H), 1.96-1.88 (m, 2H). LC-MS: m/z (ES) 272.2 (MH)+, 294.3 (MNa)+.

Fuente