Sodium ethoxide → 2-Ethoxymethyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 1643687Notes

Reaction equation

HRID 1643687 reaction equation
[CH:1]([O:4][C:5]1[C:10]2[CH2:11][CH:12]([CH2:14][O:15]S(C3C=CC(C)=CC=3)(=O)=O)[O:13][C:9]=2[CH:8]=[C:7]([C:26](=[O:34])[NH:27][C:28]2[CH:32]=[CH:31][N:30]([CH3:33])[N:29]=2)[CH:6]=1)([CH3:3])[CH3:2].[CH3:35][CH2:36][O-].[Na+]>CCO>[CH3:33][N:30]1[CH:31]=[CH:32][C:28]([NH:27][C:26]([C:7]2[CH:6]=[C:5]([O:4][CH:1]([CH3:3])[CH3:2])[C:10]3[CH2:11][CH:12]([CH2:14][O:15][CH2:35][CH3:36])[O:13][C:9]=3[CH:8]=2)=[O:34])=[N:29]1

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 59560417Toluene-4-sulfonic acid 4-isopropoxy-6-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-2,3-dihydro-benzofuran-2-ylmethyl ester

Product 1

HCID 595602872-Ethoxymethyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amideYield 36%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of toluene-4-sulfonic acid 4-isopropoxy-6-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-2,3-dihydro-benzofuran-2-ylmethyl ester (216a) (84 mg, 0.17 mmol) in anhydrous EtOH (2 mL) was added NaOEt (1.5 mL, 21% wt). The mixture was heated at 50° C. for 4 hr, then quenched with H2O and extracted with 3×EtOAc. The organic layers were washed with 2×H2O, dried over Na2SO4, and concentrated. The residue was purified by reverse phase HPLC to give a white glass (22 mg, 36% yield). 1H NMR (400 MHz, CDCl3) δ 8.99 (s, 1 H) 7.20-7.34 (m, 1 H) 7.02 (s, 1 H) 6.86 (dd, J=13.26, 1.64 Hz, 2 H) 4.92-5.09 (m, 1 H) 4.57-4.69 (m, 1 H) 3.78 (s, 3 H) 3.63-3.72 (m, 1 H) 3.54-3.62 (m, 3 H) 3.22 (dd, J=16.42, 9.60 Hz, 1 H) 2.92 (dd, J=16.29, 7.45 Hz, 1 H) 1.34 (dd, J=5.81, 1.77 Hz, 6 H) 1.23 (t, J=7.07 Hz, 3 H); LCMS for C19H25N3O4 m/z 360.20 (M+H+).

Workup

  1. customquenched with H2O
  2. extractionextracted with 3×EtOAc
  3. washThe organic layers were washed with 2×H2O
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-7aa4d94907704ca8843e2305704ba4f0
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

Loading…