Ethylene Glycol → 4-(8-Benzyl-2,8-diaza-spiro[5.5]undec-2-yl)-2-methyl-6-nitro-phenylamine

HRID 470303Notes

Reaction equation

I[C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:5]([NH2:6])=[C:4]([CH3:12])[CH:3]=1.[CH2:13]([N:20]1[CH2:25][CH2:24][CH2:23][C:22]2([CH2:30][CH2:29][CH2:28][NH:27][CH2:26]2)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(O)CO.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)C.[Cu]I>[CH2:13]([N:20]1[CH2:25][CH2:24][CH2:23][C:22]2([CH2:26][N:27]([C:2]3[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:5]([NH2:6])=[C:4]([CH3:12])[CH:3]=3)[CH2:28][CH2:29][CH2:30]2)[CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A suspension of 4-iodo-2-methyl-6-nitroaniline (1.39 g, 5 mmol), 2-benzyl-2,8-diaza-spiro[5.5]undecane (1.22 g, 5 mmol), CuI (190.5 mg, 1.0 mmol), ethylene glycol (931 mg, 15 mmol) and K3PO4 (3.2 g, 15 mmol) in isopropanol (40 mL) was sealed and heated at 90° C. for 19 h. After cooled down to room temperature, the reaction mixture was concentrated. The residue was purified by chromatography (99:1 CH2Cl2/MeOH) to afford the title compound (593 mg, 30%). 1H NMR (CDCl3) δ 1.24 (m, 2H), 1.48-1.68 (6H), 2.01-2.24 (m, 2H), 2.24 (s, 3H), 2.57 (m, 2H), 2.73 (d, J=12 Hz, 1H), 2.82 (m, 1H), 3.03 (m, 1H), 3.14 (d, J=12 Hz, 1H), 3.47 (d, J=9 Hz, 2H), 5.30 (br s, 2H NH), 7.11 (s, 1H), 7.19-7.33 (5H), 7.44 (s, 1H). ESI-MS m/z 395 (MH+).

Workup

customwas sealed
temperatureAfter cooled down to room temperature
concentrationthe reaction mixture was concentrated
customThe residue was purified by chromatography (99:1 CH2Cl2/MeOH)

Sources & evidence

ORD record: ord-48524d0e0e6247848fe88de9fd4467cf
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629147B2

Reaction notes

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