Triethylamine → N-{2-[(4S)-2-oxo-4-benzyl(1,3-oxazolidin-3-yl)]-2-oxoethyl}-N-methyl-3-phenylprop-2-ynamide

温度

-20 °C

To a −30° C. solution of 2-(N-methyl-3-phenylprop-2-ynoylamino)acetic acid (100.0 g, 0.460 mol, 1.1 equiv) and Et3N (117 mL, 0.836 mol, 2 equiv) in THF (1100 mL) was added a solution of PivCl (57 mL, 0.460 mol, 1.1 equiv) in THF (100 mL) at such a rate that the temperature was maintained below −20° C. The resulting white slurry was stirred at −20° C. Meanwhile, a −78° C. solution of (S)-(−)-4-benzyl-2-oxazolidinone (74.1 g, 0.418 mol) in THF (900 mL) was treated with a solution of n-BuLi (2.5M in hexane, 185 mL, 0.460 mol, 1.1 equiv) at such a rate that the temperature was maintained below −68° C. The reaction was stirred at −78° C. for 15 min. To this mixture was added via cannula a −78° C. solution of the mixed anhydride prepared above. The reaction was allowed to warm to −10° C. over 30 min and treated with a saturated NH4Cl solution (500 mL). The resulting mixture was concentrated under reduced pressure and the residue was partitioned between water (200 mL) and EtOAc (500 mL). The organic layer was washed with water (3×300 mL), a saturated NaHCO3 solution (2×300 mL) and a saturated NaCl solution (2×300 mL), dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (gradient from 25% to 65% EtOAc/hex) to give N-{2-[(4S)-2-oxo-4-benzyl(1,3-oxazolidin-3-yl)]-2-oxoethyl}-N-methyl-3-phenylprop-2-ynamide (119.6 g, 74%) as a white foam. Analytical data of this product was identical to Intermediate R obtained by Method 1.

1. temperaturewas maintained below −20° C
2. temperaturewas maintained below −68° C
3. stirringThe reaction was stirred at −78° C. for 15 min
4. customprepared above
5. temperatureto warm to −10° C. over 30 min
6. concentrationThe resulting mixture was concentrated under reduced pressure
7. customthe residue was partitioned between water (200 mL) and EtOAc (500 mL)
8. washThe organic layer was washed with water (3×300 mL)
9. dry with materiala saturated NaHCO3 solution (2×300 mL) and a saturated NaCl solution (2×300 mL), dried (Na2SO4)
10. concentrationconcentrated under reduced pressure
11. customThe crude product was purified by flash chromatography (gradient from 25% to 65% EtOAc/hex)

ORDレコード

ord-cea4780c7264417fbefb2d51ec48aca3

出典データセット

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06784167B2