Ammonium Hydroxide → 2-Phthalimido-4-methylpentanamide

HRID 1451844Notes

Reaction equation

HRID 1451844 reaction equation
[C:1]1(=[O:19])[N:5]([CH:6]([CH2:10][CH:11]([CH3:13])[CH3:12])[C:7](O)=[O:8])[C:4](=[O:14])[C:3]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:2]12.C(N1C=CN=C1)([N:22]1C=CN=C1)=O.[OH-].[NH4+]>O1CCCC1.O>[C:1]1(=[O:19])[N:5]([CH:6]([CH2:10][CH:11]([CH3:13])[CH3:12])[C:7]([NH2:22])=[O:8])[C:4](=[O:14])[C:3]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:2]12

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 1028082-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-methylpentanoic acid

Product 1

HCID 27872542-Phthalimido-4-methylpentanamideYield 89.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 2-phthalimido-4-methylpentanoic acid (1.32 g, 5.0 mmol) in tetrahydrofuran (25 mL) are added carbonyldiimidazole (0.81 g, 5.0 mmol) and a few crystals of 4-N,N-dimethylaminopyridine followed by 15 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature for 1 hour, then 1 mL of concentrated ammonium hydroxide is added. After 10 minutes, the reaction mixture is diluted with 50 mL water. The resulting slurry is partially concentrated to remove the tetrahydrofuran and filtered. The solid is washed with water and dried in vacuo (60° C., <1 mm) to afford 1.16 g (89%) of 2-phthalimido-4-methylpentanamide as a white powder: mp 173°-176° C.; 1H NMR (DMSO-d6, 250 MHz) δ 6 7.95-7.79 (m, 4 H, Ar), 7.61 (br s, 1 H, CONH2), 7.22 (br s, 1 H, CONH2), 4.73-4.60 (m, 1 H), 2.30-2.10 (m, 1 H), 1.95-1.80 (m, 1H), 1.45-1.25 (m, 1H); 13C NMR (DMSO-d6) δ: 170.4, 167.7, 134.4, 131.5, 123.1, 51.3, 36.4, 24.7, 23.2, 20.6. Anal. Calculated for C14H16N2O3. Theoretical: C, 64.60; H, 6.20; N, 10.76. Found: C, 64.63; H, 6.11; N, 10.70.

Workup

  1. waitAfter 10 minutes
  2. concentrationThe resulting slurry is partially concentrated
  3. customto remove the tetrahydrofuran
  4. filtrationfiltered
  5. washThe solid is washed with water
  6. customdried in vacuo (60° C., <1 mm)

Sources & evidence

ORD record
ord-0bbcfbae86a245f684cd657d8e196fec
Source dataset
uspto-grants-1997_02
Patent number
US05605914

Reaction notes

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