Iodine → HCID 67981148, compound

Participants

Reaction Conditions

Reaction Steps

Magnesium (1.86 g, 77.4 mmol) was suspended in diethyl ether (70 mL) and to the suspension was added iodine (17.8 mg, 0.07 mmol). Bromo-cyclobutane (10 g, 70 mmol) was added slowly and the mixture was refluxed for 3 h. To a solution of 4′-(trifluoromethyl)biphenyl-4-carbonitrile (300 mg, 1.21 mmol) (prepared as in Example 1.25 Step A, using 4-bromobenzonitrile) in tetrahydrofuran (3 mL) was added this prepared Grignard (334 mg, 6.06 mL in diethyl ether, 6.06 mmol) at 0° C. under nitrogen. The resulting mixture was heated in a microwave at 100° C. for 1 hr. After that time, methanol (5 mL) and sodium borohydride (91.8 mg, 2.43 mmol) were carefully added at 0° C. After stirring for 5 minutes, the reaction mixture was quenched with saturated ammonium chloride (20 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were concentrated. Purification by column chromatography (0-6% methanol/dichloromethane) gave cyclobutyl(4′-(trifluoromethyl)biphenyl-4-yl)methanamine (0.100 g, 27%) as a yellow solid. 1H NMR (400 MHz, CD3OD, δ): 7.84 (d, J=8.0, 2 H), 7.77 (dd, J=8.0, J=8.0, 4 H), 7.53 (d, J=8.0, 2 H), 4.27 (d, J=10.4, 1 H), 2.98-2.92 (m, 1 H), 2.08-2.06 (m, 1 H), 1.86-1.80 (m, 5 H).

Provenance & Evidence