Hydroxylamine → HCID 136354502, compound

Participants

Reaction Steps

Add hydroxylamine (50% solution in water, 0.128 mL, 2.09 mmol) to a solution of 3-[[4-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (950 mg, 1.90 mmol) in ethanol (20 mL) and stir. Heat solution to reflux. After 3 hours, cool to ambient temperature and concentrate to give a residue. Dissolve the residue in tetrahydrofuran (20 mL) and cool to 0° C. Add pyridine (226 mg, 2.85 mmol) and 2-ethylhexyl chloroformate (403 mg, 2.09 mmol) and stir. After 30 minutes, add water (50 mL) and extract with ethyl acetate. Combine the organic layers, dry with sodium sulfate filter and concentrate to give a residue. Dissolve the residue in xylenes (20 mL) and heat to 130° C. After 4 hours, cool to ambient temperature and concentrate under reduced pressure to give a residue. Purify the residue by flash chromatography eluting with acetone:acetic acid:hexanes (25%:1%:74%) to give a white solid. Dissolve the solid in a solution of 1% aqueous hydrochloric acid:methanol, and stir. After 1 hour, concentrate under reduced pressure to give a residue. Purify the residue by reverse phase chromatography eluting with methanol:acetic acid:water to yield the title compound as a white solid (22 mg, 2.4%): 1H NMR (DMSO-d6) δ 0.86 (t, 3H), 1.48 (sextet, 2H), 2.56 (m, 5H), 5.21 (s, 2H), 5.79 (d, 1H), 6.11 (d, 1H), 6.70 (d, 1H), 7.41 (m, 4H), 7.49 (t, 1H), 7.63 (m, 2H), 7.79 (d, 1H), 7.89 (s, 1H), 12.83 (s, 1H), 12.96 (bs, 1H); MS (esi negative) m/z (rel intensity) 473 (100).

Provenance & Evidence