Ammonium Hydroxide → HCID 21250981, compound

HRID 1421328Notes

Reaction equation

HRID 1421328 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][N:3]1[CH:11]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH3:26])[CH:17]=1)[CH2:12][C:13](O)=[O:14].C(N1C=CN=C1)([N:29]1C=CN=C1)=O.[OH-].[NH4+]>O1CCCC1>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][N:3]1[CH:11]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH3:26])[CH:17]=1)[CH2:12][C:13]([NH2:29])=[O:14]

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 183492403-(3-Ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolinyl)propanoic acid

Product 1

HCID 21250981HCID 21250981, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-(1-oxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propionic acid (12.6 g, 35.4 mmol) and 1,1'-carbonyldiimidazole (5.97 g, 36.8 mmol), in tetrahydrofuran (100 mL) was stirred for 1.5 hours at room temperature. To the solution was added ammonium hydroxide (7.5 mL, 112.5 mmol, 28-30%) and stirring was continued for 20 minutes. The tetrahydrofuran was removed in vacuo and the remaining residue was slurried in 100 mL of water for 30 minutes. The mixture was filtered and the white solid was washed with water (150 mL), air dried and dried in vacuo (60° C.,<1 mm). The resulting solid was recrystallized form ethyl acetate (1.1 L) and was then dried in vacuo (60° C.,<1 mm) to afford 9.61 g (77%) of 3-(1-oxoisoindolin2-yl)-3-(3-ethoxy-4-methoxyphenyl)propionamide as a white solid: mp 169-171.5; 1H NMR (DMSO-d6)δ 7.75-7.40 (m, 5H), 7.05-6.80 (m, 4H), 5.75 (m, 1H), 4.56 (d, J=17.6 Hz, 1H), 4.14 (d, J=17.6 Hz, 1H), 3.98 (m, 2H), 3.72 (s, 3H), 2.93 (m, 2H), 1.30 (t, J=6.9 Hz, :3H); 13C NMR (DMSO-d6)δ 171.2, 166.8, 148.3, 147.8, 141.6, 132.2, 132.1, 131.2, 127.8, 123.4, 122.7, 119.1, 112.1, 111.7, 63.6, 55.4, 51.3, 46.2, 37.8, 14.6; Anal. Calcd. for C20H22N2O5. Theoretical: C, 67.78; H, 6.26; N, 7.90. Found: C, 67.89; H, 6.31; N, 7.83.

Workup

  1. customThe tetrahydrofuran was removed in vacuo
  2. waitthe remaining residue was slurried in 100 mL of water for 30 minutes
  3. filtrationThe mixture was filtered
  4. washthe white solid was washed with water (150 mL), air
  5. customdried
  6. customdried in vacuo (60° C.,<1 mm)
  7. customThe resulting solid was recrystallized form ethyl acetate (1.1 L)
  8. customwas then dried in vacuo (60° C.,<1 mm)

Sources & evidence

ORD record
ord-f8cc439ef35a4e1d80d03a3bbe5db154
Source dataset
uspto-grants-2000_06
Patent number
US06075041

Reaction notes

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