1-Chloro-4-(chloromethyl)benzene → 2-Butoxy-3-(4-{2-[1-(4-chloro-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid

HRID 1985158Notes

Reaction equation

HRID 1985158 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Cl)=[CH:4][CH:3]=1.C([O:12][C:13](=[O:38])[C:14]([O:33][CH2:34][CH2:35][CH2:36][CH3:37])([CH3:32])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH:25]2[CH2:29][NH:28][C:27](=[O:30])[N:26]2[CH3:31])=[CH:18][CH:17]=1)C.[H-].[Na+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH2:34]([O:33][C:14]([CH3:32])([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH:25]2[CH2:29][N:28]([CH2:6][C:5]3[CH:8]=[CH:9][C:2]([Cl:1])=[CH:3][CH:4]=3)[C:27](=[O:30])[N:26]2[CH3:31])=[CH:18][CH:17]=1)[C:13]([OH:38])=[O:12])[CH2:35][CH2:36][CH3:37]

Participants

6

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 688675082-Butoxy-2-methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-propionic acid ethyl ester

Product 1

HCID 103113402-Butoxy-3-(4-{2-[1-(4-chloro-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

4-Chlorobenzyl chloride (0.04 g, 0.174 mmol) and tetrabutyl ammonium iodide (catalytic amount) are added to a 0° C. suspension of 2-butoxy-2-methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-propionic acid ethyl ester (0.047 g, 0.116 mmol) and sodium hydride (0.012 g, 0.29 mmol, 60% suspension on mineral oil), pre-stirred for 1 h at ambient temperature. The reaction mixture is stirred at ambient temperature 48 h, diluted with ethyl acetate, and washed with 1N HCl and water. The organic layer is dried, concentrated, and purified by LCMS to provide the title compound. 1H NMR (400 MHz, CDCl3): δ 7.27 (d, 2H, J=8.7 Hz), 7.17 (d, 2H, J=8.7 Hz), 7.07 (d, 2H, J=8.7 Hz), 7.71 (d, 2H, J=8.7 Hz), 4.34, 4.32 (ABq, 2H, J=15.0 Hz), 3.95 (t, 3H, J=5.9 Hz), 3.69-3.62 (m, 1H), 3.61-3.55 (m, 1H), 3.51-3.45 (m, 1H), 3.38 (t, 1H, J=8.7 Hz), 3.04-2.93 (m, 3H), 2.84 (s, 3H), 2.26-2.18 (m, 1H), 1.92-1.84 (m, 1H), 1.62-1.54 (m, 2H), 1.49 (s, 3H), 1.42-1.33 (m, 3H), 0.93 (t, 3H, J=7.3 Hz). MS [EI+] 503 (M+H)+, [EI−] 501 (M−H)+.

Workup

  1. stirringThe reaction mixture is stirred at ambient temperature 48 h
  2. washwashed with 1N HCl and water
  3. customThe organic layer is dried
  4. concentrationconcentrated
  5. custompurified by LCMS

Sources & evidence

ORD record
ord-ed4b3d9733b5463d9abdcc08e347de4b
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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