Acetic-formic anhydride → HCID 10072705, compound

HRID 658148Notes

Reaction equation

HRID 658148 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[NH:27][C:28](=[O:30])[CH3:29])[C:18]2=[O:31])[CH2:13][CH2:14][NH:15][OH:16])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[CH:32](OC(=O)C)=[O:33]>C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:17]2[C:25](=[O:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][C:23]=3[NH:27][C:28](=[O:30])[CH3:29])[C:18]2=[O:31])[CH2:13][CH2:14][N:15]([CH:32]=[O:33])[OH:16])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]

Participants

4

Reactant 2

HCID 75269Acetic-formic anhydrideHCID 86595519HCID 86595519, compound

Product 1

HCID 10072705HCID 10072705, compoundYield 24.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (1R)—N-{2-[1-(3-ethoxy-4-methoxy-phenyl)-3-hydroxyamino-propyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide (350 mg, 0.82 mmol) in methylene chloride (3 mL) was added a solution of acetyl formate (84 mg) in methylene chloride (1 mL) at 0° C. After 1 h, the mixture was extracted with ethyl acetate (25 mL) and water (25 mL). The organic layer was washed with brine (20 mL) and dried over MgSO4. The solvent was removed in vacuo. The residue was purified with prep HPLC to give (1R)—N-{2-[1-(3-ethoxy-4-methoxy-phenyl)-3-(N-formyl-N-hydroxy-amino)-propyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide as a white solid (90 mg, 24% yield): mp: 96-98° C.; 1H NMR (CDCl3) δ 1.46 (t, J=7 Hz, 3H, CH3), 2.26 (s, 3H, CH3), 2.81-2.83 (m, 2H, CH2), 3.56 (t, J=6 Hz, 2H, CH2), 3.85 (s, 3H, CH3), 4.10 (q, J=7 Hz, 2H, CH2), 5.25 (t, J=8 Hz, 1H, NCH), 6.82 (d, J=8 Hz, 1H, Ar), 7.06-7.09 (m, 2H, Ar), 7.45 (d, J=8 Hz, 1H, Ar), 7.64 (t, J=8 Hz, 1H, Ar), 7.72 (s, 1H, CH), 8.75 (d, J=8 Hz, 1H, Ar), 9.49 (s, 1H, NH); 13C NMR (CDCl3) δ 14.73, 24.95, 28.35, 46.61, 51.92, 55.93, 64.46, 111.37, 112.79, 115.21, 118.05, 120.63, 124.90, 130.33, 131.09, 136.02, 137.47, 148.48, 149.40, 155.73, 167.72, 169.27, 170.07; Anal Calcd for C23H25N3O7+0.3 H2O: C, 59.95; H, 5.60; N, 9.12; H2O, 1.17. Found: C, 59.94; H, 5.59; N, 8.98; H2O, 1.22.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (25 mL) and water (25 mL)
  2. washThe organic layer was washed with brine (20 mL)
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed in vacuo
  5. customThe residue was purified with prep HPLC

Sources & evidence

ORD record
ord-a8b208b9e3354ba6bdb84e2f06c51668
Source dataset
uspto-grants-2011_12
Patent number
US08076369B2

Reaction notes

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