Hydrochloric Acid → Ethyl 4-(2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy)-3-oxobutanoate

HRID 652076Notes

Reaction equation

HRID 652076 reaction equation
[H-].[Na+].[C:3]1(=[O:16])[N:7]([CH2:8][CH2:9][OH:10])[C:6](=[O:11])[C:5]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:4]12.Cl[CH2:18][C:19](=[O:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].Cl>O1CCCC1.C(OCC)(=O)C>[CH2:24]([O:23][C:21](=[O:22])[CH2:20][C:19]([CH2:18][O:10][CH2:9][CH2:8][N:7]1[C:6](=[O:11])[C:5]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:4]2[C:3]1=[O:16])=[O:26])[CH3:25]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 69484Ethyl 4-chloroacetoacetateHCID 77499N-(2-Hydroxyethyl)phthalimide

Product 1

HCID 9840027Ethyl 4-(2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy)-3-oxobutanoateYield 97.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a slurry of sodium hydride (57% dispersion in oil, 66.1 g; 1.57M), in tetrahydrofuran (500 ml) cooled to 0° under nitrogen was added 2-phthalimidoethanol (150 g; 0.785M) followed by ethyl 4-chloroacetoacetate (129 g; 0.785M) in tetrahydrofuran (250 ml) over 1 hour. The mixture was stirred at room temperature overnight then poured into a mixture of 1M hydrochloric acid (800 ml) and ethyl acetate (750 ml). The organic phase was separated and the solvent was evaporated at reduced pressure. The residue separated into two layers and the upper layer of mineral oil was removed to leave the title compound (243 g) as a crude product which was used without further purification.

Workup

  1. customThe organic phase was separated
  2. customthe solvent was evaporated at reduced pressure
  3. customThe residue separated into two layers
  4. customthe upper layer of mineral oil was removed

Sources & evidence

ORD record
ord-4b91a98b50e04d7d9652228f73707e14
Source dataset
uspto-grants-1987_06
Patent number
US04670449

Reaction notes

Loading…