Trifluoroacetic acid → (3S)-3-(1-methylethyl)-1-[3-(methyloxy)-4-nitrophenyl]piperazine

HRID 419673Notes

Reaction equation

[CH3:1][CH:2]([C@H:4]1[CH2:9][N:8]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([O:19][CH3:20])[CH:11]=2)[CH2:7][CH2:6][N:5]1C(OC(C)(C)C)=O)[CH3:3].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:3][CH:2]([C@@H:4]1[NH:5][CH2:6][CH2:7][N:8]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([O:19][CH3:20])[CH:11]=2)[CH2:9]1)[CH3:1]

Participants

Conditions

Temperature: 0 °C

Procedure

1,1-Dimethylethyl (2S)-2-(1-methylethyl)-4-[3-(methyloxy)-4-nitrophenyl]-1-piperazinecarboxylate (0.482 g, 1.27 mmol) was dissolved in 20 mL of DCM with stirring. TFA (4.0 mL, 52 mmol) was added, and the reaction was stirred for 4 h. The reaction was cooled to 0° C. and slowly quenched with 40 mL of 3N NaOH (aq.). The mixture was poured into H2O and DCM, and the layers were separated. The aqueous layer was washed with DCM. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to afford the title compound of step E (0.356 g, 1.27 mmol, 100%). 1H NMR (400 MHz, DMSO-d6) δ 7.86 (d, J=9.5 Hz, 1H), 6.57 (dd, J=9.5, 2.6 Hz, 1H), 6.46 (d, J=2.6 Hz, 1H), 3.88 (s, 3H), 3.77-3.86 (m, 2H), 2.93-3.02 (m, 1H), 2.82 (td, J=11.9, 3.3 Hz, 1H), 2.54-2.71 (m, 2H), 2.29-2.39 (m, 1H), 2.22 (br. s., 1H), 1.55-1.67 (m, 1H), 0.94 (d, J=6.8 Hz, 3H), 0.92 (d, J=6.8 Hz, 3H).

Workup

stirringthe reaction was stirred for 4 h
customslowly quenched with 40 mL of 3N NaOH (aq.)
additionThe mixture was poured into H2O and DCM
customthe layers were separated
washThe aqueous layer was washed with DCM
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-b8e9a178a31240968a66f3925c468eb8
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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