(3,3-Dimethylcyclobutyl)methanamine hydrochloride synthesis

Yield:1455037-07-6 61%

Reaction Conditions:

Stage #1: 3,3-dimethylcyclobutanecarboxamidewith borane-THF in tetrahydrofuran at 65;
Stage #2: with hydrogenchloride in methanol at 65;

Steps:

92 Synthesis of (3,3-dimethylcyclobutyl)methanamine hydrochloride

Add a solution 3,3-dimethylcyclobutanecarboxamide (0.438 g, 3.44 mmol) in THF (20 mL) to borane (1.0M in THF, 35 mL, 35.0 mmol) and heat to 65°C overnight. Cool to RT, quench with the careful addition of MeOH (35 mL) and concentrate to dryness. Dissolve the residue in MeOH (35 mL), treat slowly with 3M HCI (35 mL) and heat at 65°C overnight. Cool to RT, concentrate under high vacuum to near-dryness and co-evaporate with IPA (4x) to afford a white solid. Triturate the solid with EtOAc, collect via filtration, rinse with a small amount of EtOAc and dry to afford the title compound (317 mg, 61%) as a white solid. 1H NMR (400 MHz, DMSO-d₆): δ 7.88 (s, 2 H); 2.77 (d, J = 7.5 Hz, 2 H); 2.43 (m, 1 H); 1.79 (m, 2 H); 1.51 (m, 2 H); 1.09 (s, 3 H); 1.02 (s, 3 H); MS(ESI) m/z: 114.2 (M+H⁺).

References:

WO2013/134298,2013,A1 Location in patent:Page/Page column 62