Chloroacetyl chloride → N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazine-8-carboxamide

N-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-amino-2-hydroxybenzamide 24b (830 mg, 2.1 mmol) was dissolved in 10 ml of DMF and at 0° C. TEA (0.58 ml, 2 equiv.) and chloroacetyl chloride (0.2 ml, 1.2 equiv.) were added. The mixture was stirred at rt for 2 hours. K2CO3 (580 mg, 2 equiv.) was added and the reaction was stirred at rt for 20 hours. The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column using AcOEt 1/petroleum ether 1 as eluant gave 460 mg of a white solid. Yield=50% 1HNMR (DMSO, 200 MHz) δ 1.57 (2H, bs), 1.69 (4H, bs), 2.84 (4H, m), 4.58 (2H, d, J=5.2 Hz), 4.69 (2H, s), 7.03 (2H, m), 7.30 (2H, m), 7.45 (2H, m), 8.70 (1H, bt), 10.85 (1H, bs); [M+1] 434.1 (C22H22F3N3O3 requires 433.4).

1. stirringthe reaction was stirred at rt for 20 hours
2. customThe solvent was evaporated
3. dissolutionthe crude was dissolved in AcOEt (30 ml)
4. washwashed with water (1×20 ml) and brine
5. dry with materialThe organic phase was dried over sodium sulfate
6. concentrationconcentrated under vacuum
7. customThe purification of the crude residue by chromatographic column

ORD record

ord-5c667cb36c544955b791ead3a639f50b

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216975B2