Trifluoroacetic acid → 1-(3-Methoxy-4-nitrophenyl)piperazine

To a solution of tert-butyl 4-(3-methoxy-4-nitrophenyl)piperazine-1-carboxylate (18a; 1.66 g, 4.92 mmol) in 5 mL of DCM at RT was added TFA (3.65 mL, 49.2 mmol) and the resulting mixture was stirred at RT for 2 h. It was concentrated under reduced pressure. The yellow residue was partitioned between 200 mL of EtOAc and 25 mL of 1 N NaOH. The layers were separated and the organic solution was washed with 25 mL of brine, dried over sodium sulfate and concentrated to give 1-(3-methoxy-4-nitrophenyl)piperazine, m/z (ESI, +ve ion) 238.1 (M+H)+. The yellow residue was dissolved in 100 mL of DCM, cooled with and ice bath, treated with triethylamine (1.37 mL, 9.84 mmol) followed by acetyl chloride (0.38 mL, 5.41 mmol). After 1 h at 0° C., it was treated with 25 mL of 0.5 N NaOH. The layers were separated and the aqueous was extracted with 50 mL of DCM. The combined DCM solution was washed with 25 mL of brine, dried over Na2SO4 and concentrated to give 1-(4-(3-methoxy-4-nitrophenyl)piperazin-1-yl)ethanone (20a) as a yellow crystalline solid. Crude material was used in the next step. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.91 (1H, d, J=9.4 Hz), 6.59 (1H, dd, J=9.4, 2.3 Hz), 6.54 (1H, d12.3 Hz), 3.92 (3H, s), 3.59 (4H, d, J=2.7 Hz), 3.51-3.56 (2H, m), 3.43-3.50 (2H, m), 2.05 (3H, s).

1. concentrationIt was concentrated under reduced pressure
2. customThe yellow residue was partitioned between 200 mL of EtOAc and 25 mL of 1 N NaOH
3. customThe layers were separated
4. washthe organic solution was washed with 25 mL of brine
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated

ORD record

ord-6b674f3ad13d4823808f8c93ef10bb2d

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346801B2