1,8-Diazabicyclo(5.4.0)undec-7-ene → 6-Allyl-6-(4-fluorophenyl)-3-((1-phenylpiperidin-4-yl)methyl)-1,3-oxazinan-2-one

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Reaction Steps

3-(4-fluorophenyl)-1-((1-phenylpiperidin-4-yl)methylamino)hex-5-en-3-ol (120 mg, 0.314 mmol) was dissolved in THF (30 mL) and pyridine (c.a. 500 μL, excess). A solution of triphosgene (60 mg, excess) in THF (5 mL) was added slowly in 4 batches. After stirring 4 h at rt, DBU (94 μL, 2 equiv.) was added and the mixture was heated to reflux for overnight. There was still a lot of starting material on LC-MS spectra. The mixture was concentrated, redissolved in EtOAc (40 mL), washed with 5% aq HCl (2×8 mL), brine (8 mL), and dried over Na2SO4. After filtration and concentration, the residue was purified by prep HPLC to afford 6-allyl-6-(4-fluorophenyl)-3-((1-phenylpiperidin-4-yl)methyl)-1,3-oxazinan-2-one (17 mg, 13%). LC-MS Method 1 tR=1.32 min, m/z=409 (M+1); 1H NMR (CD3OD) 7.62-7.53 (m, 4H), 7.39 (m, 2H), 7.13 (t, 2H), 5.67 (m, 1H), 5.04 (dd, 2H), 3.05 (m, 2H), 2.63 (d, 2H), 2.57 (d, 1H), 2.32 (m, 1H), 2.06 (m, 1H).

Provenance & Evidence