Methyl 3-isocyanatobenzoate → methyl-3-[3-(4-isopropylphenyl)-2,5-DIOXO-imidazolidin-1-yl]-benzoate

HRID 2194818

Reaction equation

HRID 2194818 reaction equation
CO[C:3](=[O:15])[CH2:4][NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([CH3:14])[CH3:13])=[CH:8][CH:7]=1.[N:16]([C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=1)[C:22]([O:24][CH3:25])=[O:23])=[C:17]=[O:18]>C1(C)C=CC=CC=1>[CH3:25][O:24][C:22](=[O:23])[C:21]1[CH:26]=[CH:27][CH:28]=[C:19]([N:16]2[C:3](=[O:15])[CH2:4][N:5]([C:6]3[CH:7]=[CH:8][C:9]([CH:12]([CH3:13])[CH3:14])=[CH:10][CH:11]=3)[C:17]2=[O:18])[CH:20]=1

Participants

4

Reactant 2

HCID 2733366Methyl 3-isocyanatobenzoateHCID 22669181Methyl-2-(4-isopropylanilino)acetate

Product 1

HCID 66603600methyl-3-[3-(4-isopropylphenyl)-2,5-DIOXO-imidazolidin-1-yl]-benzoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of methyl-2-(4-isopropylanilino)acetate (1.10 g, 5.31 mmol) in toluene (30 mL) was treated with methyl 3-isocyanatobenzoate (1.03 g), and the resulting solution was stirred at ambient temperature for 20 h. The reaction mixture was evaporated, and a portion (0.6 g) of the resulting solid material used directly in the next step. The compound was dissolved in methanol, and treated with sodium methoxide (0.84 mL of 0.5 M in methanol). The resulting solution was stirred for 1 h, then evaporated and partitioned between water and ethyl acetate (50 mL each). The organic extract was washed with brine, dried over magnesium sulfate, filtered and evaporated. The residual material was separated by preparative thin-layer chromatography (silica gel, 30:70 ethyl acetate-hexane) to afford pure product, methyl-3-[3-(4-isopropylphenyl)-2,5-DIOXO-imidazolidin-1-yl]-benzoate, as a waxy solid. 1H NMR (CDCl3, 300 MHz): δ 8.16 (1H, t, J=1.8 Hz), 8.07 (1H, dt, J=7.6, 1.5 Hz), 7.67 (1H, ddd, J=8.0, 2.0, 1.1 Hz), 7.56 (1H, t, J=7.9 Hz), 7.51 (2H, d, J=8.8 Hz), 7.27 (2H, d, J=8.8 Hz), 4.47 (2H, s), 3.92 (3H, s), 2.91 (1H, m, J=7.0 Hz), 1.25 (6H, d, J=7.0 Hz). Mass spectrum (ES+): m/z 353 (36), 321 (100).

Workup

  1. customThe reaction mixture was evaporated
  2. dissolutionThe compound was dissolved in methanol
  3. additiontreated with sodium methoxide (0.84 mL of 0.5 M in methanol)
  4. stirringThe resulting solution was stirred for 1 h
  5. customevaporated
  6. custompartitioned between water and ethyl acetate (50 mL each)
  7. extractionThe organic extract
  8. washwas washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe residual material was separated by preparative thin-layer chromatography (silica gel, 30:70 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-681b4d5f567f41959067b30a94a6281e
Source dataset
uspto-grants-2012_12
Patent number
US08334313B2

Linked notes

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