반응 #305608

반응 방정식

H2O

5-chloropentanoyl chloride

(1S,2S)-pseudoephedrine

triethylamine

→

5-chloro-N-((1S,2S)-1-hydroxy-1-phenylpropan-2-yl)-N-methylpentanamide

수율 93.4%

용매

THF

THF

반응 조건

후처리

1. 1
   농축the resulting mixture was concentrated to ˜10% of the original volume
2. 2
   기타The resulting solution was partitioned between H2O/EtOAc
3. 3
   기타the layers were separated
4. 4
   추출The aqueous layer was extracted with EtOAc (600 mL)
5. 5
   세척The combined organic layers were washed with saturated aqueous NaHCO3, brine
6. 6
   건조dried over MgSO4
7. 7
   여과filtered
8. 8
   농축concentrated under reduced pressure
9. 9
   기타to furnish the crude product as pale yellow oil
10. 10
    기타The crude amide was purified by flash chromatography (ISCO; 3×330 g column; CH2Cl2 to 5% MeOH/CH2Cl2)
11. 11
    기타to provide the product as a clear, viscous oil
12. 12
    기타The residual MeOH was removed
13. 13
    기타through azeotroping with toluene (3×100 mL)

실험 절차

To a magnetically stirred solution of (1S,2S)-pseudoephedrine (60 g, 363.1 mmol) in THF (600 mL) at room temperature was added triethylamine (65.4 mL, 472 mmol) in one portion. The resulting white suspension was cooled to 0° C. A solution of 5-chloropentanoyl chloride (49 mL, 381 mmol) in THF (130 mL) was added dropwise to the mixture over 45 min using an addition funnel. The mixture was then allowed to stir at 0° C. for 30 min. H2O (40 mL) was added and the resulting mixture was concentrated to ˜10% of the original volume. The resulting solution was partitioned between H2O/EtOAc and the layers were separated. The aqueous layer was extracted with EtOAc (600 mL). The combined organic layers were washed with saturated aqueous NaHCO3, brine, dried over MgSO4, filtered, and concentrated under reduced pressure to furnish the crude product as pale yellow oil. The crude amide was purified by flash chromatography (ISCO; 3×330 g column; CH2Cl2 to 5% MeOH/CH2Cl2) to provide the product as a clear, viscous oil. The residual MeOH was removed through azeotroping with toluene (3×100 mL) to provide 5-chloro-N-((1S,2S)-1-hydroxy-1-phenylpropan-2-yl)-N-methylpentanamide (96.2 g, 339 mmol, 93%). LCMS (m/z=266.0)

출처