Reacción #1148657

Ecuación de reacción

NaHCO3

p-Toluenesulfonylchloride

HCl

pyridine

pTSA H2O

→

(2S-trans)-2-hydroxymethyl-4-[[(4-methylphenyl)sulfonyl]oxy]-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas then added in portions over a 10 minute period
2. 2
   Extracciónextracted with methylene chloride (3×200 mL)
3. 3
   Secadothe organics were dried over anhydrous sodium sulfate
4. 4
   workup.DISSOLUTIONThe crude tosylate intermediate was dissolved in THF (50 mL), to which
5. 5
   workup.ADDITIONwas added H2O (0.5 mL)
6. 6
   Extracciónextracted with methylene chloride (3×50 mL)
7. 7
   SecadoThe combined organics were dried over sodium sulfate
8. 8
   OtroThe crude alcohol was purified by flash chromatography on SiO2 eluting with acetone/chloroform (0-5-10% acetone)

Procedimiento

2a(2) (3.41 g, 10.3 mmol) was dissolved in anhydrous pyridine (30.0 mL) and cooled to 0° C. p-Toluenesulfonylchloride (5.89 g, 30.9 mmol) was then added in portions over a 10 minute period. The flask was then placed in a refrigerator at 4° C. for 48 h. The resulting solution was poured into 1 N HCl (300 mL), extracted with methylene chloride (3×200 mL) and the organics were dried over anhydrous sodium sulfate. The crude tosylate intermediate was dissolved in THF (50 mL), to which was added H2O (0.5 mL) followed by pTSA-H2O (1.03 mmol). Once the reaction was complete as determined by TLC, the mixture was poured into saturated aqueous NaHCO3 (150 mL) and extracted with methylene chloride (3×50 mL). The combined organics were dried over sodium sulfate. The crude alcohol was purified by flash chromatography on SiO2 eluting with acetone/chloroform (0-5-10% acetone) to give 2.71 g (71% for 2-steps) of (2S-trans)-2-hydroxymethyl-4-[[(4-methylphenyl)sulfonyl]oxy]-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester (2a(3)) as a clear oil:

Fuente