Formaldehyde → HCID 11740318, compound

Participants

Reaction Conditions

Reaction Steps

Solution A was prepared by adding (3S)-3-(4-aminophenoxy)-1-[(1,3-benzodioxol-5-yl)methyl]piperidine (4.4 g, 13.5 mmol) and NH4OH (1.2 mL, 15 mmol) in methanol, and diluting with methanol to 10 mL. Solution B was prepared by adding formaldehyde (1.01 mL, 13.5 mmol) and 40% solution glyoxal, and then diluting with THF to 10 mL. Solution A and solution B were added simultaneously to water (6.0 mL, pre-heated to 65° C.) with stirring over a 30 min period. The resulting mixture was then heated to 65° C. for 2 hours. After removal of the solvent in vacuo, the residual oil was dissolved in CH2Cl2 (100 mL), washed with water (50 mL×3), brine (50 mL), and dried (NaSO4). Purification by column chromatography (ethyl acetate/methanol 100:1) afforded (3S)-3-[4-(imidazol-1-yl)phenoxy]-1-[(1,3-benzodioxol-5-yl)methyl]piperidine (3.7 g, 72.5% yield), NMR: (DMSO-d6) 9.1 (s, 1), 7.90 (t, 1), 7.65–7.62 (m, 2), 7.56 t, 1), 7.32 (d, 1), 7.24–7.21 (m, 2), 7.10 (d, 1), 6.98 (d, 1), 5.98 (d, 2), 5.00 (m, 1), 4.28 (d, 1), 4.18 (d, 1), 3.40 (d, 1), 3.12 (m, 1), 3.09–2.98 (m, 2), 2.05–1.88 (m, 3), 1.72 (m, 1) ppm.

Provenance & Evidence