Formic Acid → 3-((2(RS)-(Phenoxymethyl)morpholin-4-yl)methyl)-quinoline Hydrogen Oxalate

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Quinoline-3-carboxaldehyde (447 mg, 2.8 mmol), 2(RS)-(phenoxymethyl)morpholine (500 mg, 2.59 mmol) and anhydrous formic acid (0.1 ml) were heated at 120° C. (oil bath temperature), with stirring, for 6 hours. The reaction mixture was cooled, 2M hydrochloric acid (20 ml) added and the solution washed with ethyl acetate (20 ml). The aqueous was basified to pH=11 with 2M aqueous sodium hydroxide, then extracted with ethyl acetate (2×30 ml). The combined organics were dried (sodium sulphate) then evaporated to give a gum which was purified by column chromatography on silica (200 g) using ethyl acetate to ethyl acetate/methanol (25:1) to afford the title compound free base as a pale yellow gum (340 mg, 36%). The hydrogen oxalate salt had mp 164°-166° C. (ethanol/water). MS CI+, m/z=335 for (M+H)+. 1H NMR (360 MHz, DMSO-d6) δ2.23 (1H, dd, J1 =J2 ==11 Hz), 2.35 (1H, ddd, J1 =3, J2 =J3 =11 Hz), 2.80 (1H, d, J=11 Hz), 2.97 (1H, d, J=11 Hz), 3.61 (1H, ddd, J1 =2, J2 =J3 =11 Hz), 3.80-3.92 (4H, m), 3.96 (2H, d, J=5 Hz), 6.89-6.94 (3H, m), 7.23-7.28 (2H, m), 7.59-7.64 (1H, m), 7.73-7.78 (1H, m), 7.97-8.04 (2H, m), 8.29 (1H, d, J=2 Hz), 8.90 (1H, d, J=2 Hz). Found: C, 63.38; H, 5.84; N, 6.48. C21H22N2O2.C2H2O4.0.5H2O requires C, 63.73; H, 5.81; N, 6.46%.

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