Dimethylformamide → 3-(4-{2-[1-(4-Hydroxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-isopropoxy-propionic acid ethyl ester

HRID 1985262Notes

Reaction equation

HRID 1985262 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH:5]([O:14][CH:15]([CH3:17])[CH3:16])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:2].[CH3:19][N:20]1[CH:24]([CH2:25][CH2:26]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:23][N:22]([CH2:38][C:39]2[CH:44]=[CH:43][C:42](C(F)(F)F)=[CH:41][CH:40]=2)[C:21]1=[O:49].CN(C=[O:54])C>>[CH2:1]([O:3][C:4](=[O:18])[CH:5]([O:14][CH:15]([CH3:17])[CH3:16])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:26][CH2:25][CH:24]2[CH2:23][N:22]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([OH:54])=[CH:41][CH:40]=3)[C:21](=[O:49])[N:20]2[CH3:19])=[CH:11][CH:12]=1)[CH3:2]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 22926879Ethyl 3-(4-hydroxyphenyl)-2-isopropoxypropanoateHCID 86596229HCID 86596229, compound

Product 1

HCID 688699793-(4-{2-[1-(4-Hydroxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-isopropoxy-propionic acid ethyl esterYield 67%

Conditions

Temperature
65 °C

Procedure

A mixture of 3-(4-hydroxy-phenyl)-2-isopropoxy-propionic acid ethyl ester (0.034 g, 0.134 mmol), toluene-4-sulfonic acid 2-[3-methyl-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethyl ester (0.068 g, 0.149 mmol) and CS2CO3 (0.066 g, 0.202 mmol) in DMF (6 mL) was heated to 65° C. under N2 for 16 h. The reaction was cooled and quenched with 1 N HCl (10 mL) and worked up extractively with Et2O and water. The organic layer was dried (MgSO4) and the solvent removed in vacuo to afford crude product that was purified by flash chromatography using 4:1 hexanes:acetone to afford 0.048 g (67%) 3-(4-{2-[1-(4-hydroxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-isopropoxy-propionic acid ethyl ester. Rf=0.36 (1:1 hexanes:acetone). 1H NMR (500 MHz, CDCl3)δ 1H NMR (500 MHz, CDCl3) □ 7.56 (d, 2H, J=8.07 Hz), 7.36 (d, 2H, J=8.07 Hz), 7.13 (d, 2H, J=8.80 Hz), 6.72 (d, 2H, J=8.80 Hz), 4.47, 4.36 (ABq, 2H, J=15.16 Hz), 4.20-4.12 (m, 2H), 4.00-3.94 (m, 3H), 3.66-3.59 (m, 1H), 3.48 (hp, 1H, J=5.87 Hz), 3.37 (t, 1H, J=8.80 Hz), 2.98 (t, 1H, J=8.80 Hz), 2.90-2.85 (m, 2H), 2.84 (s, 3H), 2.27-2.23 (m, 1H), 1.93-1.84 (m, 1H), 1.23 (t, 3H, J=6.85 Hz), 1.14 (d, 3H, J=5.87 Hz), 0.97 (d, 3H, J=5.87 Hz). MS (ES+) Calc'd for C28H36N2O5F3 (M+1) 537. Found m/z 537 (100%).

Workup

  1. temperatureThe reaction was cooled
  2. customquenched with 1 N HCl (10 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customthe solvent removed in vacuo
  5. customto afford crude product that
  6. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-9b1aebe368074a73b5f44adfff987e86
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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