Methanol → 4-(Azetidin-1-ylcarbonyl)-1-[1-(diphenylmethyl)azetidin-3-yl]piperidine

HRID 426085Notes

Reaction equation

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

Participants

Conditions

Temperature: 120 °C

Procedure

To a mixture of 4-(azetidin-1-ylcarbonyl)piperidine (0.34 g, 2.0 mmol) and 1-(diphenylmethyl)azetidin-3-one (see Bioorg. Med. Chem. Lett.; 13; 2003; 2191-2194, 0.37 g, 1.6 mmol), methanol (5 mL) and acetic acid (0.1 mL) was added (polystyrylmethyl)trimethylammonium cyanoborohydride (4.1 mmol/g, 0.61 g). The reaction mixture was heated for 10 min at 120° C. using microwave single node heating and then filtered through a phase separator. The solvent was removed by evaporation and the product was purified by chromatography on silica gel (methanol-methylene chloride, 5:95). There was obtained 0.42 g (70%) of 4-(azetidin-1-ylcarbonyl)-1-[1-(diphenylmethyl)azetidin-3-yl]piperidine as a colorless foam. 1H NMR (500 MHz, CDCl3): 1.6-1.7 (m, 2H), 1.7-1.8 (m, 4H), 2.0-2.1 (m, 1H), 2.2 (qn, 2H), 2.7-2.8 (m, 2H), 2.8-3.0 (m, 3H), 3.4 (t, 2H), 4.0 (t, 2H), 4.1 (t, 2H), 4.4 (s, 1H), 7.1-7.2 (t, 2H), 7.2-7.3 (t, 4H), 7.4 (d, 4H); LCMS: m/z 390 (M+1)+.

Workup

temperatureheating
filtrationfiltered through a phase separator
customThe solvent was removed by evaporation
customthe product was purified by chromatography on silica gel (methanol-methylene chloride, 5:95)

Sources & evidence

ORD record: ord-c85cc7b8bae648228f559095eea964d8
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106208B2

Reaction notes

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