Dimethylformamide → Methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinate

HRID 714291Notes

Reaction equation

HRID 714291 reaction equation
[O:1]=[C:2]1[NH:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=1)[C:10]([O-:12])=[O:11].[H-].[Na+].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1.[CH3:27]N(C)C=O>>[F:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:6]2[CH2:5][CH2:4][N:3]([C:7]3[CH:8]=[C:9]([CH:13]=[CH:14][N:15]=3)[C:10]([O:12][CH3:27])=[O:11])[C:2]2=[O:1])=[CH:21][CH:22]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 866530512-(2-Oxoimidazolidin-1-yl)isonicotinate

Product 1

HCID 58247772Methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinateYield 67%

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(2-oxoimidazolidin-1-yl)isonicotinate (10.00 g, 45.20 mmol) in N,N-dimethylformamide (300 mL) was added sodium hydride (60% dispersion in mineral oil, 1.90 g, 45.20 mmol) at 0° C. The resulting solution was stirred for 30 minutes at 0° C., followed by the addition of 1-(bromomethyl)-4-fluorobenzene (8.54 g, 45.20 mmol). The reaction mixture was warmed to ambient temperature, stirred for 17 hours and concentrated in vacuo to dryness. The residue was purified by column chromatography eluted with dichloromethane and ethyl acetate to give methyl 2-(3-(4-fluorobenzyl)-2-oxoimidazolidin-1-yl)isonicotinate as a colorless solid (10.03 g, 67%): mp 119-121° C.; 1H NMR (300 MHz, CDCl3) δ 8.87 (d, J=0.6 Hz, 1H), 8.35 (d, J=5.4 Hz, 1H), 7.45-7.43 (m, 1H), 7.29-7.25 (m, 2H), 7.04-6.98 (m, 2H), 4.44 (s, 2H), 4.20 (t, J=7.8 Hz, 2H), 3.91 (s, 3H), 3.35 (t, J=7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 165.9, 164.0, 160.7, 156.8, 153.4, 148.0, 138.7, 132.3, 130.0, 116.7, 115.8, 115.5, 112.5, 52.6, 47.8, 41.3, 41.0; MS (ES+) m/z 330.2 (M+1).

Workup

  1. temperatureThe reaction mixture was warmed to ambient temperature
  2. stirringstirred for 17 hours
  3. concentrationconcentrated in vacuo to dryness
  4. customThe residue was purified by column chromatography
  5. washeluted with dichloromethane and ethyl acetate

Sources & evidence

ORD record
ord-b9d62e2632b54e3b8ee6c3df05df23c4
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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