Dichloromethane → 3-(2-Tert-butoxycarbonylamino-ethylamino)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester

HRID 1890407Notes

Reaction equation

HRID 1890407 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]([N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]1=[O:16])=[CH2:5].C(=O)([O-])[O-].[K+].[K+].[C:24]([O:28][C:29](=[O:34])[NH:30][CH2:31][CH2:32][NH2:33])([CH3:27])([CH3:26])[CH3:25].ClCCl>C(#N)C>[CH3:1][O:2][C:3](=[O:17])[CH:4]([N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]1=[O:16])[CH2:5][NH:33][CH2:32][CH2:31][NH:30][C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:34]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 187201N-BOC-ethylenediamineHCID 599143Methyl 2-(1,3-dioxoisoindol-2-yl)prop-2-enoate

Product 1

HCID 669298353-(2-Tert-butoxycarbonylamino-ethylamino)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl esterYield 32.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 12.60 g (51.38 mmol) of 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acrylic acid methyl ester (described in Synthetic Communications, 33(8), 1375-1382; 2003) dissolved in 170 mL of acetonitrile was added at room temperature 42.60 g (308.28 mmol) of potassium carbonate and 9.05 g (56.52 mmol) of (2-amino-ethyl)-carbamic acid tert-butyl ester. The resulting mixture was stirred at room temperature for 12 h. 300 mL of dichloromethane was added and the mixture was filtered and the solid obtained was triturated with dichloromethane, filtered, and the resulting filtrates were evaporated to dryness. The residue was dissolved in diethyl ether, washed with a saturated aqueous solution of sodium hydrogen carbonate, saturated aqueous solution of sodium chloride, dried over sodium sulfate and evaporated to dryness. The residue was chromatographed on silica gel eluting with a mixture of chloroform/methanol/aqueous ammonia solution (29%) in the proportions 98/2/0.2 led to afford 6.50 g (31%) of the desired compound.

Workup

  1. filtrationthe mixture was filtered
  2. customthe solid obtained
  3. customwas triturated with dichloromethane
  4. filtrationfiltered
  5. customthe resulting filtrates were evaporated to dryness
  6. dissolutionThe residue was dissolved in diethyl ether
  7. washwashed with a saturated aqueous solution of sodium hydrogen carbonate, saturated aqueous solution of sodium chloride
  8. dry with materialdried over sodium sulfate
  9. customevaporated to dryness
  10. customThe residue was chromatographed on silica gel eluting with a mixture of chloroform/methanol/aqueous ammonia solution (29%) in the proportions 98/2/0.2

Sources & evidence

ORD record
ord-23fd94016b3f43a381aa43faacdc8027
Source dataset
uspto-grants-2013_08
Patent number
US08507476B2

Reaction notes

Loading…