Ammonium Acetate → (1S,5S)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-amine

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Reaction Steps

To a solution of (1S,5S)-1-(1-naphthyl)bicyclo[3.1.0]hexan-3-one (0.7 g, 3.1 mmol) in methanol (87.5 mL) was added ammonium acetate (24.3 g, 310 mmol), stirred for 15 minutes at room temperature and sodium cyanoborohydride (1.58 g, 25 mmol) was added and the mixture was heated to 60° C. for 2 hours. The reaction was monitored by TLC (ethyl acetate/methanol/triethylamine (89:10:1)). The reaction mixture was concentrated under reduced pressure to remove methanol at 30° C., the crude mass was quenched with water (50 mL). The aqueous layer was extracted with ethyl acetate (3×150 mL). The aqueous layer was saturated with sodium chloride and re-extracted with ethyl acetate (3×150 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to yield 2.4 g of crude oil, which was purified by preparative HPLC to 400 mg (57%) of 99% pure product. 1H NMR δ(300 MHz,CD3OD): 1.1-1.15 (1H,m), 1.21-1.24 (1H,m), 1.88-1.93 (2H,m), 2.24-2.31 (1H,m), 2.45-2.57 (1H,m), 2.90-2.92 (1H,m), 4.10-4.2 (1H,m), 7.37-7.57 (4H,m), 7.74-7.76 (1H,d, 6 Hz), 7.85-7.88 (1H,d,9 Hz), 8.20-8.29 (1H,m). 13CNMR (CD3OD): 140.74, 140.30, 135.51, 133.93, 129.81, 128.64, 127.76, 127.12, 127.01, 126.74, 126.59, 125.67 119.93, 54.97, 43.08, 40.42, 36.16, 34.53, 33.91, 25.88, 24.94, 23.70, 15.76. Purity: 98.5% (a/a) by HPLC. MS, M+(224).

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