Cyclopropanecarbonyl chloride → HCID 10364105, compound

HRID 853976Notes

Reaction equation

HRID 853976 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH2:24][CH3:25])[CH:16]=1)[CH2:13][CH3:14])[CH2:7]2.[CH:26]1([C:29](Cl)=[O:30])[CH2:28][CH2:27]1>C1COCC1>[CH2:24]([O:23][C:17]1[CH:16]=[C:15]([CH:12]([N:8]2[C:9](=[O:11])[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[NH:1][C:29]([CH:26]3[CH2:28][CH2:27]3)=[O:30])[CH2:7]2)[CH2:13][CH3:14])[CH:20]=[CH:19][C:18]=1[O:21][CH3:22])[CH3:25]

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 22177153HCID 22177153, compound

Product 1

HCID 10364105HCID 10364105, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 7-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-propyl]-2,3-dihydro-isoindol-1-one (1.0 g, 2.9 mmol) and cyclopropanecarbonyl chloride (0.32 mL, 3.5 mmol) in THF (10 mL) was heated to reflux for 40 min. The solvent was removed in vacuo. The residue was extracted with ethyl acetate (50 mL) and sodium hydrogen carbonate (sat, 50 mL). The organic layer was washed with brine (50 mL) and dried over MgSO4. The solvent was removed in vacuo and the residue was purified with chromatography (Silica Gel) to cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (900 mg, 76% yield): mp, 107-109° C.; 1H NMR (CDCl3) δ 0.84-0.92 (m, 2H, CH2), 0.99 (t, J=7 Hz, 3H, CH3), 1.02-1.13 (, 2H, CH2), 1.44 (t, J=7 Hz, 3H, CH3), 1.64-1.73 (m, 1H, CH), 2.00-2.16 (m, 2H, CH2), 3.86 (s, 3H, CH3), 4.00 (d, J=17 Hz, 1H, CHH), 4.09 (q, J=7 Hz, 2H, CH2), 4.27 (d, J=17 Hz, 1H, NCHH), 5.33 (dd, J=7, 9 Hz, 1H, NCH), 6.83-6.95 (m, 3H, Ar), 7.00 (d, J=8 Hz, 1H, Ar), 7.42 (t, J=8 Hz, 1H, Ar), 8.42 (d, J=8 Hz, 1H, Ar), 10.67 (s, 1H, NH); 13C NMR (CDCl3) δ 8.19, 11.18, 14.78, 16.18, 24.54, 45.64, 55.53, 55.97, 64.58, 111.46, 112.91, 116.68, 117.67, 119.51, 131.96, 132.94, 138.02, 141.37, 148.54, 149.04, 169.55, 172.70; Anal Calcd for C24H28N2O4: C, 70.57; H, 6.91; N, 6.86. Found: C, 70.54; H, 6.91; N, 6.86.

Workup

  1. temperatureto reflux for 40 min
  2. customThe solvent was removed in vacuo
  3. extractionThe residue was extracted with ethyl acetate (50 mL) and sodium hydrogen carbonate (sat, 50 mL)
  4. washThe organic layer was washed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-1e6528cc36014f8398690cbe2cd3dae9
Source dataset
uspto-grants-2007_08
Patent number
US07256210B2

Reaction notes

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