4-Piperidinecarboxylic acid → 1-[1-(Diphenylmethyl)azetidin-3-yl]piperidine-4-carboxylic acid

HRID 426087

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3][CH2:2]1.[C:10]1([CH:16]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:17]2[CH2:20][C:19](=O)[CH2:18]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([BH3-])#N.C[NH+](C)C>CO.C(O)(=O)C>[C:10]1([CH:16]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:17]2[CH2:20][CH:19]([N:1]3[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=[O:8])[CH2:3][CH2:2]3)[CH2:18]2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a mixture of piperidine-4-carboxylic acid (0.13 g, 1.0 mmol) and 1-(diphenylmethyl)azetidin-3-one (see Bioorg. Med. Chem. Lett.; 13; 2003; 2191-2194, 0.24 g, 1.0 mmol), methanol (3 mL) and acetic acid (0.3 mL) was added (polystyrylmethyl) trimethylammonium cyanoborohydride (4.1 mmol/g, 0.25 g). The reaction mixture was heated for 5 min at 120° C. using microwave single node heating. Methanol was added and then the resin was filtered off. The solvent was removed by evaporation. There was obtained 0.35 g (100%) of 1-[1-(diphenylmethyl)azetidin-3-yl]piperidine-4-carboxylic acid. 1H NMR (500 MHz, CDCl3): 1.6-1.8 (m, 2H), 1.9-2.0 (m, 4H), 2.3-2.4 (m, 1H), 2.7-2.8 (m, 2H), 2.9-3.0 (m, 3H), 3.4 (t, 2H), 4.4 (s, 1H), 7.2 (t, 2H), 7.2-7.3 (t, 4H), 7.4 (d, 4H); LCMS: m/z 351 (M+1)+.

Workup

temperatureheating
filtrationthe resin was filtered off
customThe solvent was removed by evaporation

Sources & evidence

ORD record: ord-fd7f1818e1554c7e9d900b182ca95aba
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106208B2

Linked notes

Loading…