Sodium borohydride → HCID 42602278, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(1-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-1,3-dihydroisobenzofuran-1-yl)propanenitrile (190 mg, 0.44 mmol) and nickel(II) chloride hexahydrate (158 mg, 0.66 mmol) in methanol (4 mL) at 0° C. was added sodium borohydride (117 mg, 3.1 mmol) in several portions over 30 minutes. The ice bath was removed and stirring continued for 1 h. Very clean and mostly complete conversion to product (by LC/MS) was observed. The reaction was cooled to 0° C. and treated with concentrated hydrochloric acid (85 μL). After 5 min, celite was added, and the mixture was filtered. The solution was made basic by addition of solid sodium bicarbonate, and filtered again. The organics were concentrated to give the crude amine which was purified by column chromatography (10% MeOH/DCM-->10:90:0.5 MeOH/DCM/Me3N in EtOH) to give 114 mg (59%) as a colorless oil. 1H-NMR (CDCl3, 300 MHz) δ 7.73 (s, 1H), 7.63 (s, 2H), 7.05-7.40 (m, 4H), 5.11 (s, 2H), 4.61 (qAB, JAB=13.1 Hz, 2H), 3.66 (s, 2H), 2.64 (m, 2H), 1.70-2.10 (m, 4H), 1.50 (m, 1H), 1.20 (m, 1H); 13C-NMR (CDCl3, 126 MHz) δ 141.42, 141.39, 140.1, 131.7 (q, J=33.6 Hz), 128.1, 127.5, 127.1, 123.4 (q, J=273 Hz), 121.6, 121.4, 121.1, 90.3, 76.8, 72.9, 72.0, 42.3, 34.1, 27.3. Mass spec.: 434.25 (MH)+. Accurate mass spec.: m/z 434.1542 [MH]+, Δ=1.3 ppm.

Provenance & Evidence