Triethylamine → 3-[(2-Tert-butoxycarbonylamino-ethyl)-ethoxycarbonyl-amino]-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester

HRID 1890408Notes

Reaction equation

HRID 1890408 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH:4]([N:17]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:27])[CH2:5][NH:6][CH2:7][CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C(N(CC)CC)C.Cl[C:37]([O:39][CH2:40][CH3:41])=[O:38].[Cl-].[NH4+]>ClCCl>[CH3:1][O:2][C:3](=[O:28])[CH:4]([N:17]1[C:18](=[O:27])[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:25]1=[O:26])[CH2:5][N:6]([CH2:7][CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:14])[CH3:15])=[O:11])[C:37]([O:39][CH2:40][CH3:41])=[O:38]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 669298353-(2-Tert-butoxycarbonylamino-ethylamino)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester

Product 1

HCID 669299233-[(2-Tert-butoxycarbonylamino-ethyl)-ethoxycarbonyl-amino]-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl esterYield 90.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 18.80 g (47.54 mmol) of 3-(2-tert-butoxycarbonylamino-ethylamino)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester dissolved in 156 mL of anhydrous dichloromethane was added 8.02 mL (57.05 mmol) of triethylamine. The resulting mixture was cooled at 0° C. and 5.00 mL (52.29 mmol) of ethyl chloroformate dissolved in 30 mL of anhydrous dichloromethane was added. The resulting mixture was stirred at room temperature for 12 h. Saturated aqueous solution of ammonium chloride was added and the mixture extracted with dichloromethane. The extracts were washed with a saturated aqueous solution of sodium chloride, sodium carbonate, dried over sodium sulfate and evaporated to dryness. The residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 99/1 led to afford 20.00 g (90%) of the desired compound as an oil.

Workup

  1. additionwas added
  2. extractionthe mixture extracted with dichloromethane
  3. washThe extracts were washed with a saturated aqueous solution of sodium chloride, sodium carbonate
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe residue was chromatographed on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 99/1

Sources & evidence

ORD record
ord-4a03025e88e04858918655b988c1364e
Source dataset
uspto-grants-2013_08
Patent number
US08507476B2

Reaction notes

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