Phthalimide → (2R)-(t-butyloxycarbonylamino)-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester

HRID 2187972Notes

Reaction equation

HRID 2187972 reaction equation
[H-].[Na+].[C:3]1(=[O:13])[NH:7][C:6](=[O:8])[C:5]2=[CH:9][CH:10]=[CH:11][CH:12]=[C:4]12.[C:14]([O:18][C:19](=[O:33])[C@H:20]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:22][CH2:23]I)([CH3:17])([CH3:16])[CH3:15]>CN(C)C=O.C1OCCOCCOCCOCCOCCOC1>[C:14]([O:18][C:19](=[O:33])[C@H:20]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:22][CH2:23][N:7]1[C:3](=[O:13])[C:4]2[C:5](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:6]1=[O:8])([CH3:15])([CH3:16])[CH3:17]

Participants

6

Reactant 3

HCID 6809PhthalimideHCID 24758Sodium hydrideHCID 15479355N-Boc-5-Iodo-D-norvaline tert-butyl ester

Product 1

HCID 15549668(2R)-(t-butyloxycarbonylamino)-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (0.522 g,13.05 mmol) is added to a solution of phthalimide (2.33 g, 15.84 mmol) and 18-crown-6 (0.01 g) in 20 mL of N,N-dimethylformamide (DMF). After stirring at RT for 20 min, a solution of the title F compound, (2R)-(t-butyloxycarbonylamino)-5-iodopentanoic acid t-butyl ester (4.61 g,11.55 mmol) in 5 mL of DMF is added, and the solution is stirred at RT for 30 min, then at 60° C. for 8 h. The solvent is removed under reduced pressure, and the residue is partitioned between 300 mL of ethyl acetate and 225 mL of 0.05M aqueous HCl. The organic phase is washed with 100 mL water and 50 mL of brine, dried over anhydrous Na2SO4 and concentrated to give 4.83 g (100%) of (2R)-(t-butyloxycarbonylamino)-5-(1,3-dioxo-1,3-dihydroisoindol-2-yl)pentanoic acid t-butyl ester as a tan solid: NMR(CDCl3) 1.43 (s, 9H), 1.45 (s, 9H), 1.60-1.88 (m, 4H), 3.71 (t, 2H, J=6.6), 4.18-4.26 (m, 1H), 5.06 (br d, 1H, J=7.9), 7.70-7.73 (m, 2H), 7.83-7.86 (m, 2H); IR 1712, 1500, 1155; ESI-MS 290 (M++1).

Workup

  1. stirringthe solution is stirred at RT for 30 min
  2. waitat 60° C. for 8 h
  3. customThe solvent is removed under reduced pressure
  4. customthe residue is partitioned between 300 mL of ethyl acetate and 225 mL of 0.05M aqueous HCl
  5. washThe organic phase is washed with 100 mL water and 50 mL of brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3ca4c4b7ac874d9396f5d97c1d13b921
Source dataset
uspto-grants-2002_06
Patent number
US06410580B1

Reaction notes

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