4-Methylmorpholine → 1-(Di(pyridin-3-yl)methyl)piperazine

HRID 2278172Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[N:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)[CH:2]=1.CN1CCOCC1.[Si](I)(C)(C)C>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]([C:21]2[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=2)[N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:2]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A round bottom flask was charged with tert-butyl 4-(di(pyridin-3-yl)methyl)piperazine-1-carboxylate (220 mg, 0.621 mmol), CH2Cl2 (20 mL), and NMM (136 μL, 1.23 mmol). The reaction was cooled to 0° C. and TMSI (106 μL, 0.745 mmol) was added dropwise. After 10 min at 0° C., additional TMSI (100 μL, 0.700 mmol) was added. After stirring 10 min at 0° C. the reaction was allowed to warm to room temperature. After 15 min at room temperature the reaction was diluted in CH2Cl2 and washed (1×) sat Na2CO3. The organics were dried (Na2SO4), filtered, and concentrated and yielded 103 mg crude product (0.406 mmol, 65%) as a yellow oil, which was used without further purification in the next step. 1H NMR 400 MHz (CDCl3) δ 8.64 (d, J=2.4 Hz, 2H), 8.47 (dd, J=4.8, 1.6 Hz, 2H), 7.70 (dt, J=8.0, 2.0 Hz, 2H), 7.23 (dd, J=7.9, 4.8 Hz, 2H), 4.36 (s, 1H), 2.91 (t, J=4.9 Hz, 4H), 2.38 (t, J=5.0 Hz, 5H). LCMS (ESI, m/z): 255 [M+H]+.

Workup

temperatureto warm to room temperature
washwashed (1×)
dry with materialThe organics were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-15d7cb58a88a4920b955f437e39f58e4
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133148B2

Reaction notes

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