Formic Acid → 1-Methyl-4-(4-nitrophenyl)piperazine

Temperature

120 °C

To 4-(4′-nitrophenyl)piperazine hydrochloride (1.00 g, 4.10 mmol) was added formic acid (1.55 mL, 41.0 mmol) and 37% aq. formaldehyde (3.06 mL, 41.0 mmol) in a microwave vessel and the reaction was heated at 120° C. for 3 minutes. To the cooled reaction mixture was added EtOAc (100 mL) and 2 M aq. NaOH (70 mL). The layers were separated and the organic layer was washed with brine (50 mL), the layers were separated and the aqueous brine layer was extracted with EtOAc (50 mL), the organic layers were combined and dried (Na2SO4), filtered and concentrated in vacuo to give the crude product which was purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-60% methanol (containing 1% ammonia solution) in EtOAc) to give the title compound (I11) (0.636 g, 70% yield) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 8.07-8.01 (m, 2H), 7.05-6.99 (m, 2H), 3.48-3.40 (m, 4H), 2.46-2.39 (m, 4H), 2.21 (s, 3H). LCMS Method C: rt 1.45 min; m/z 222.2 [M+H]+.

1. customTo the cooled reaction mixture
2. customThe layers were separated
3. washthe organic layer was washed with brine (50 mL)
4. customthe layers were separated
5. extractionthe aqueous brine layer was extracted with EtOAc (50 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give the crude product which
10. customwas purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-60% methanol (containing 1% ammonia solution) in EtOAc)

ORD record

ord-85b4d860e3914aafad63fcada5fc6c54

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09421205B2