تفاعل #305608

معادلة التفاعل

H2O

5-chloropentanoyl chloride

(1S,2S)-pseudoephedrine

triethylamine

→

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

المردود 93.4%

المذيبات

THF

THF

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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)

المصدر