Cesium carbonate → 1-Tert-butyl 3-ethyl 3-((4-methoxybenzylamino)methyl)piperidine-1,3-dicarboxylate

HRID 513100Notes

Reaction equation

I[CH2:2][C:3]1([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][NH2:30])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1>[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][NH:30][CH2:2][C:3]2([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]2)=[CH:25][CH:24]=1

Participants

Conditions

Temperature: 145 °C

Procedure

1-tert-butyl 3-ethyl 3-(iodomethyl)piperidine-1,3-dicarboxylate (C1) (4.13 mmol, 1.64 g) was dissolved in THF (5 mL), (4-methoxyphenyl)methanamine (6.19 mmol, 0.81 mL) and cesium carbonate (6.19 mmol, 2.02 g) were added and the mixture was heated for 8 h at 145° C. in the microwave. The mixture was filtered over a PE-filter and concentrated in vacuo. The crude was purified by flash chromatography (heptane/EtOAc: 0 to 45% yielding the title compound (C2) (340 mg, 20%). 1H NMR (400 MHz, DMSO, 300K): δ=1.23 (3H, t, J=7.2 Hz), 1.43 (9H, s), 1.55 (2H, m), 1.67 (1H, m), 1.89 (1H, m), 2.64 (1H, d, J=11.9 Hz), 2.77 (1H, d, J=11.9 Hz), 3.21 (1H, m), 3.51 (2H, m), 3.62 (1H, m), 3.70 (2H, m), 3.79 (3H, s), 4.14 (2H, q, J=7.2 Hz), 6.84 (2H, d, J=8.6 Hz), 7.20 (2H, d, J=8.6 Hz).

Workup

filtrationThe mixture was filtered over a PE-filter
concentrationconcentrated in vacuo
customThe crude was purified by flash chromatography (heptane/EtOAc

Sources & evidence

ORD record: ord-78bb5d4aa56e44f891030458a27f88be
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102676B2

Reaction notes

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