4-Toluenesulfonyl chloride → HCID 21971397, compound

Participants

Reaction Steps

The title compound was prepared in an analogous manner to that in Example 29. NaH (60% dispersion in mineral oil, 77.8 mmol) was reacted at room temperature with phenylacetonitrile and (R)-3-bromo-O-p-toluenesulfonyl-2-methyl-1-propanol that was prepared by reacting (R)-(-)-3-bromo-2-methyl-1-propanol (33 mmol) with p-toluenesulfonyl chloride (39 mmol) in pyridine for 17 h. The afforded 1-phenyl-3-methylcyclobutanecarbonitrile contained 75% of the cis isomer and 25% of the trans isomer. In order to separate the two isomers, the allylester of the acid was prepared. 1-Phenyl-3-methylcyclobutanecarboxylic acid (24 mmol) was refluxed with neat SOCl2 (25 mL) for 1 h. SOCl2 was then evaporated, the residue was dissolved in toluene and allylalcohol (26 mmol) and pyridine (26 mmol) were added. The mixture was stirred overnight to give allyl 1-phenyl-3-methylcyclobutanecarboxylate that was chromatographed on silica gel containing 2% AgNO3 using a gradient of hexane up to hexane-EtOAc 95:5 as eluent. 1.3 g of allyl 1-phenyl-3-trans-methylcyclobutanecarboxylate was obtained. The allyl ester was then hydrolysed with KOH as described above. The obtained product contained 10% of the cis isomer. The total yield was 0.66 g (11%); 1H NMR (CDCl3) δ 1.09 (d, 3H), 2.15-2.30 (m, 1H), 2.38-2.48 (m, 2H), 2.65-2.75 (m, 2H), 7.21-7.41 (m, 5H).

Provenance & Evidence