Acetic Acid → HCID 57893614, compound

Participants

Reaction Steps

Combine 2-chloro-4-fluoro-N-[3-(2-methyl-piperidin-4-yloxy)-phenyl]-benzamide cis isomer 1 (example 57, 0.26 g, 0.72 mmol), dichloromethane (20 mL), and 37% aqueous formaldehyde (0.58 mL, 7.2 mmol) with stirring. After 10 min., add glacial acetic acid (0.08 mL, 1.44 mmol) followed by sodium triacetoxyborohydride (0.23 g, 1.08 mmol). After 3 hr., partition between 1M aqueous sodium hydroxide solution (50 mL) and dichloromethane (50 mL). Separate the organic layer, wash with aqueous NaCl solution, dry over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 10% (2M ammonia/methanol) in dichloromethane to obtain of the title compound (0.46 g, 85%). Mass spectrum: Obs. m/z 377.1443; Calc. m/z 377.1432; mp: 152° C.

Provenance & Evidence