Acetic Acid → HCID 11951998, compound

Participants

Reaction Steps

3-Azetidinyl methyl ether hydrochloride (275) (MacKenzie et al., PCT Int Appl. WO 9605193, 1996) (0.60 g, 4.9 mmol) was added to a stirred solution of propanal 75 (1.2 g, 4.9 mmol) in MeOH (100 mL) at 0° C. and the solution stirred for 30 min. NaCNBH3 (1.5 g, 24 mmol) was added and the solution stirred at 0° C. for 30 min and then HOAc (2 mL) was added and the mixture was stirred at 20° C. for 16 h. The solvent was evaporated and the residue was partitioned between DCM (200 mL) and water (200 mL). The aqueous phase was extracted with DCM (2×200 mL), the combined organic phase was dried and the solvent evaporated. The residue was purified by chromatography, eluting with 10% MeOH/EtOAc, to give 1-oxide 82 (930 mg, 60%) as a yellow oil: 1H NMR δ 8.24 (s, 1H, H-9), 7.74 (s, 1H, H-5), 4.27-4.39 (m, 3H, CH2N, CHO), 3.49-3.53 (m, 2H, CH2N), 3.30 (s, 3H, OCH3), 3.21-3.27 (m, 2H, CH2N), 3.09-3.16 (m, 4H, H-6, H-8), 3.05 (t, J=7.2 Hz, 2H, CH2), 2.14-2.26 (m, 4H, H-7, CH2); 13C NMR δ 163.9, 155.1, 149.3, 147.3, 132.3, 122.7, 144.2, 68.3, 60.9, 58.7, 56.6, 56.5, 33.5, 33.1, 32.8, 25.7, 23.8; HRMS calcd for C17H22N4O2 (M+) m/z 314.1743, found 314.1742.

Provenance & Evidence