4-Toluenesulfonyl chloride → Toluene-4-sulfonic acid 3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl ester

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Reaction Steps

To a stirring solution of [3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutyl]-methanol (0.56 g, 2.3 mmol) prepared above in 5 mL of dichlormethane was added triethyl amine (1.6 mL, 2.7 mmol) followed by 4-(dimethyl amino)pyridine (2.8 mg, 0.23 mmol) and p-toluene sulfonyl chloride (0.52 g, 2.7 mmol). After 1 hr the reaction was quenched with a saturated aqueous solution of NaHCO3. The reaction was diluted and extracted with dichloromethane. The organic layers were dried over magnesium sulfate, filtered through a fritted funnel, and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography, using a 40 g ISCO column, eluting with a gradient of 4%, 6%, and 10% MeOH/CH2Cl2. The product containing fractions were collected and concentrate under reduced pressure to give the title compound (0.82 g, 93% yield) as a colorless oil and a mixture of cis:trans isomers.

Provenance & Evidence