3-Nitrophthalic anhydride → 3-(3-Nitrophthalimido)-3-(3-ethoxy-4-methoxyphenyl)propanenitrile

HRID 1531893Notes

Reaction equation

HRID 1531893 reaction equation
[N+:1]([C:4]1[CH:14]=[CH:13][CH:12]=[C:6]2[C:7]([O:9][C:10](=[O:11])[C:5]=12)=O)([O-:3])=[O:2].[NH2:15][CH:16]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH2:29][CH3:30])[CH:21]=1)[CH2:17][C:18]#[N:19]>C(O)(=O)C.C(Cl)Cl>[N+:1]([C:4]1[CH:14]=[CH:13][CH:12]=[C:6]2[C:7]([N:15]([CH:16]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH2:29][CH3:30])[CH:21]=3)[CH2:17][C:18]#[N:19])[C:10](=[O:11])[C:5]=12)=[O:9])([O-:3])=[O:2]

Participants

5

Reactant 2

HCID 216313-Nitrophthalic anhydrideHCID 221771543-Amino-3-(3-ethoxy-4-methoxyphenyl)propanenitrile

Product 1

HCID 212509633-(3-Nitrophthalimido)-3-(3-ethoxy-4-methoxyphenyl)propanenitrileYield 56%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred suspension of 3-nitrophthalic anhydride (0.24 g, 1.13 mmol) and 3-amino-3-(3-ethoxy-4-methoxyphenyl)propanenitrile (0.25 g, 1.13 mmol) in 6 mL of acetic acid was heated to reflux under nitrogen for 12 hours. The acetic acid was removed in vacuo to afford an orange gum which was dissolved in methylene chloride (10 mL) and was washed with a saturated aqueous solution of sodium bicarbonate (2×10 mL). The organic layer was separated and the aqueous layer was extracted with methylene chloride (10 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo to afford a yellow oil. The crude product was purified by flash column chromatography (silica gel, 5% ethyl acetate/methylene chloride) and the resulting solid was dried in vacuio (60° C., <1 mm) to afford 0.25 g (56%) of 3-(3-nitrophthalimido)-3-(3-ethoxy-4-methoxyphenyl)propanenitrile as a yellow solid: mp 155.5-157° C.; 1H NMR (CDCl3) δ8.20-8.09 (m, 2H), 8.02-7.86 (m, 1H), 7.15-7.02 (m, 2H), 6.88-6.76 (m, 1H), 5.64 (dd, J=6.3, 10.6 Hz, 1H), 4.09 (q, J=7 Hz, 2H), 3.85 (s, 3H), 3.84 (dd, J=10.6, 16.7 Hz, 1H), 3.26 (dd, J=6.3, 16.7 Hz, 1H), 1.46 (t, J=7 Hz, 3H); 13C NMR (CDCl3) δ165.3, 162.3, 150.1, 148.7, 144.9, 135.7, 133.5, 129.0, 128.1, 127.4, 123.2, 120.3, 116.6, 112.1, 111.5, 64.6, 55.9, 51.9, 20.9, 14.7; Anal. calcd for C20H17N3O6. Theoretical: C, 60.76; H, 4.33; N, 10.63. Found: C, 60.59; H, 4.22; N, 10.65.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen for 12 hours
  3. customThe acetic acid was removed in vacuo
  4. customto afford an orange gum which
  5. washwas washed with a saturated aqueous solution of sodium bicarbonate (2×10 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with methylene chloride (10 mL)
  8. dry with materialThe combined organic extracts were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto afford a yellow oil
  12. customThe crude product was purified by flash column chromatography (silica gel, 5% ethyl acetate/methylene chloride)
  13. customthe resulting solid was dried in vacuio (60° C., <1 mm)

Sources & evidence

ORD record
ord-b73c7c1ba14447f29250d045669ab88c
Source dataset
uspto-grants-2001_03
Patent number
US06200987B1

Reaction notes

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