Tris(1,1-dimethylethyl)phosphine → 1-[4-(4-Amino-3-methyl-5-nitro-phenyl)-piperazin-1-yl]-ethanone

HRID 970347Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([NH2:11])=[C:4]([CH3:12])[CH:3]=1.[C:13]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)(=[O:15])[CH3:14].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:11][C:5]1[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]([N:19]2[CH2:20][CH2:21][N:16]([C:13](=[O:15])[CH3:14])[CH2:17][CH2:18]2)=[CH:3][C:4]=1[CH3:12]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-bromo-2-methyl-6-nitro-phenylamine (5 g, 21.64 mmol), 1-acetylpiperazine (4.2 g, 32.46 mmol), palladium acetate (244 mg, 1.08 mmol), tri-tert-butylphosphine (440 mg, 2.16 mmol) and sodium tert-butoxide (4.2 g, 43.29 mmol) in toluene (70 mL) was heated to 100° C. for 14 h under nitrogen. The reaction mixture was cooled to room temperature and diluted with EtOAc. After extraction, the combined organic layers were washed with water, brine, dried over Na2SO4. Concentration gave a brownish residue which was purified by flash column chromatography (10% MeOH/CH2Cl2) to yield the title compound (4.21 g, 70%). 1H NMR (400 MHz, CD3OD) δ 7.42 (1H, d, J=2.8 Hz), 7.23 (1H, d, J=2.8 Hz), 3.71 (2H, t, J=5.1 Hz), 3.67 (2H, t, J=5.1 Hz), 3.04 (2H, t, J=5.2 Hz), 2.98 (2H, t, J=5.2 Hz), 2.24 (3H, s), 2.31 (3H, s). LCMS (M+H)+ m/z 279 (t=1.46 min.).

Workup

temperatureThe reaction mixture was cooled to room temperature
extractionAfter extraction
washthe combined organic layers were washed with water, brine
dry with materialdried over Na2SO4
concentrationConcentration
customgave a brownish residue which
customwas purified by flash column chromatography (10% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-68ee9370413f40adbe9a54d91e8cf793
Source dataset: uspto-grants-2007_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07312215B2

Reaction notes

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