(-)-Epichlorohydrin → HCID 86650521, compound

Participants

Reaction Steps

To a bi-phasic mixture of 2-ethyl-4-(5-{3-[(ethyl-methyl-amino)-methyl]-5-methyl-phenyl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenol (1.74 g, 4.76 mmol) in isopropanol (100 mL) and 3M aq. NaOH (23 mL), (R)-epichlorohydrin (4.40 g, 47.6 mmol) is added. The mixture is stirred at rt for 16 h before it is concentrated to about half its volume. The remaining solution is extracted with EA, the org. extract is washed with 1M aq. NaOH followed by water. The washings are extracted back with EA. The combined org. extracts are dried over Na2SO4, filtered and concentrated. The crude product is purified by prep. HPLC (Waters XBridge Prep C18, 50×150 mm ID, 10 μm, eluting with a gradient of MeCN in water containing 0.5% of sat. aq. ammonia) to give ethyl-{3-[3-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-5-methyl-benzyl}-methyl-amine as a colourless resin (950 mg). LC-MS*: tR=1.26 min; [M+1]+=422.23; 1H NMR (D6-DMSO): δ 1.06 (t, J=7.0 Hz, 3H), 1.24 (t, J=7.5 Hz, 3H), 2.14 (s, 3H), 2.36 (s, 3H), 2.41-2.48 (m, 5H), 2.69-2.78 (m, 3H), 2.86 (t, J=5.0 Hz, 1H), 3.37-3.42 (m, 1H), 3.54 (s, 2H), 3.69 (dd, J=11.0, 6.8 Hz, 1H), 4.21 (dd, J=11.3, 2.5 Hz, 1H), 7.47 (s, 1H), 7.80 (s, 2H), 7.90 (s, 1H), 7.92 (s, 1H).

Provenance & Evidence