PMGB

To a suspension of NaH (17.6 g, 60%) in DMF (150 mL) at ice-bath temperature with mechanical stirring was added over a one hour period a mixture of 4-chlorobenzyl cyanide (30.3 g) and 1,3-dibromopropane (22.3 mL, 44.5 g). The reaction mixture was stirred for an additional 1 hour, and isopropyl alcohol (10 mL) was added slowly to quench excess NaH. Water (150 mL) was added. The reaction mixture was extracted with MTBE (2 × 200 mL), and the combined extracts were washed with water (3 × 200 mL), brine, and dried over MgSO₄. The solvent was removed in rotavapor and the final product was purified by column chromatography to give 1-(4-chlorophenyl)cyclobutanecarbonitrile (32.6 g, 85%) as a pale yellow oil. NMR complies.

Note: 1. The procedure was taken from US patent 6,974,838 B2. But we found anhydrous DMF (stored over molecular sieves) is a better solvent than DMSO in this case. 2. The reaction is very exothermic when the starting materials were added to NaH in DMF at 0 oC. The addition should be very slow in order to avoid foaming and overflow.