Phthalic Anhydride → (2S)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid tert-butyl ester

HRID 419682Notes

Reaction equation

HRID 419682 reaction equation
Cl.[C:2]([O:6][C:7](=[O:11])[C@H:8]([CH3:10])[NH2:9])([CH3:5])([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.[C:21]1(=O)[O:26][C:24](=[O:25])[C:23]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:22]12>C1(C)C=CC=CC=1.CCOCC>[C:2]([O:6][C:7](=[O:11])[C@@H:8]([N:9]1[C:24](=[O:25])[C:23]2[C:22](=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:21]1=[O:26])[CH3:10])([CH3:5])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 6811Phthalic AnhydrideHCID 81531DiisopropylethylamineHCID 11275390tert-Butyl alaninate hydrochloride

Product 1

HCID 13005797(2S)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid tert-butyl esterYield 90%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

A suspension of (2S) alanine tert-butyl ester hydrochloride (2.05 g, 11.2 mmol), diisopropylethylamine (1.83 mL, 10.6 mmol) and phthalic anhydride (1.48 g, 10 mmol) in toluene (10 mL) was refluxed for 3 hours under Dean-Stark conditions. The reaction was cooled to room temperature, diluted with Et2O, washed with 1N HCl and then with aq.sat. NaHCO3. The organic layer was dried (MgSO4), filtered and evaporated to afford the sub-title compound as a white powder (2.465 g, 90%): 1H NMR (400 MHz CDCl3) δ 1.45 (9H, s), 1.68 (3H, d), 4.90 (1H, q), 7.75 (2H, d), 7.88 (2H, d).

Workup

  1. temperaturewas refluxed for 3 hours under Dean-Stark conditions
  2. washwashed with 1N HCl
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-7080ca3fd18f490992ab57905ba4463c
Source dataset
uspto-grants-2012_01
Patent number
US08093392B2

Reaction notes

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