Dimethyl Carbonate → 1-ethyl-5-(2-methyl-[1,3]dioxolan-2-yl)-2-oxo-2,3-dihydro-1H-indole-3-carboxylic acid methyl ester

HRID 610073Notes

Reaction equation

HRID 610073 reaction equation
[Na].[C:2](=O)([O:5]C)[O:3][CH3:4].[CH2:8]([N:10]1[C:18]2[C:13](=[CH:14][C:15]([C:19]3([CH3:24])[O:23][CH2:22][CH2:21][O:20]3)=[CH:16][CH:17]=2)[CH2:12][C:11]1=[O:25])[CH3:9]>CO>[CH3:4][O:3][C:2]([CH:12]1[C:13]2[C:18](=[CH:17][CH:16]=[C:15]([C:19]3([CH3:24])[O:20][CH2:21][CH2:22][O:23]3)[CH:14]=2)[N:10]([CH2:8][CH3:9])[C:11]1=[O:25])=[O:5]

Participants

5

Reactant 3

HCID 12021Dimethyl CarbonateHCID 5360545SodiumHCID 13770532HCID 13770532, compound

Product 1

HCID 538933521-ethyl-5-(2-methyl-[1,3]dioxolan-2-yl)-2-oxo-2,3-dihydro-1H-indole-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium (2.68 g, 112 mmol) was added to methanol (110 mL) in a 3-neck flask fitted with a reflux condenser, while controlling the temperature with an ice-bath. After dissolution dimethyl carbonate (9.4 mL, 112 mmol) was added followed by 1-ethyl-5-(2-methyl-[1,3]dioxolan-2-yl)-1,3-dihydro-indol-2-one (U.S. Pat. No. 4,686,224, 9.2 g, 37 mmol). The mixture was heated to reflux for 70 hours, then cooled, concentrated to about 25 mL, diluted with water, acidified to pH 7 with acetic acid and extracted twice with ethyl acetate. The combined extracts were washed with brine, dried over magnesium sulfate and concentrated in vacuo to an oily solid which was triturated in isopropyl ether, collected and dried (7.9 g, 70%).

Workup

  1. customfitted with a reflux condenser
  2. additionwas added
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 70 hours
  5. temperaturecooled
  6. concentrationconcentrated to about 25 mL
  7. additiondiluted with water
  8. extractionextracted twice with ethyl acetate
  9. washThe combined extracts were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo to an oily solid which
  12. customwas triturated in isopropyl ether
  13. customcollected
  14. customdried (7.9 g, 70%)

Sources & evidence

ORD record
ord-4c60cda229f048c9bf371e2d8f2003d5
Source dataset
uspto-grants-1999_12
Patent number
US05998463

Reaction notes

Loading…