Reaction Steps
(4-(Tetrahydrofuran-3-ylsulfonyl)phenyl)(1-(trifluoromethyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)methanone was subjected to chiral SFC (column: Phenomenex Lux Cellulose-2 (250×10 mm), 5 μm; mobile phase: 40% IPA w/0.2% DEA, 60% CO2; concentration: 30 mg/mL in MeOH; injection volume: 20 μA; pressure: 100 bar; detection wavelength: 254 nm) to give two peaks. For each enantiomer, the solvent was evaporated and the residue was dissolved in ethyl acetate. The solution was washed with aqueous 1M hydrochloric acid (1×1 mL), a saturated aqueous solution of sodium bicarbonate (1×1 mL) and a saturated aqueous solution of sodium chloride (1×1 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure to yield [4-[(3S)-tetrahydrofuran-3-yl]sulfonylphenyl]-[1′-(trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone as a yellow solid (peak 1, the stereochemistry was randomly assigned): ESI-MS m/z calc. 546.1. found 547.2 (M+1)+; Retention time: 1.93 minutes (3 min run); NMR (400 MHz, DMSO) δ 7.99 (d, J=8.4 Hz, 2H), 7.74 (d, J=8.3 Hz, 2H), 7.57 (d, J=8.0 Hz, 1H), 7.37-7.14 (m, 3H), 7.03 (d, J=3.9 Hz, 1H), 6.40 (d, J=4.0 Hz, 1H), 4.53-4.36 (m, 1H), 4.33-4.19 (m, 1H), 4.08-3.94 (m, 1H), 3.91-3.58 (m, 3H), 3.56-3.16 (m, 3H), 2.19-1.82 (m, 6H) and [4[(3R)-tetrahydrofuran-3-yl]sulfonylphenyl]-[1′-(trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone as a yellow solid (peak 2, the stereochemistry was randomly assigned): ESI-MS m/z calc. 546.1. found 547.2 (M+1)+; Retention time: 1.93 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 7.99 (d, J=8.3 Hz, 2H), 7.74 (d, J=8.3 Hz, 2H), 7.57 (d, J=8.2 Hz, 1H), 7.36-7.14 (m, 3H), 7.03 (d, J=3.9 Hz, 1H), 6.40 (d, J=4.0 Hz, 1H), 4.54-4.36 (m, 1H), 4.33-4.17 (m, 1H), 4.09-3.95 (m, 1H), 3.90-3.59 (m, 3H), 3.58-3.12 (m, 3H), 2.24-1.77 (m, 6H).
