Diethyl Ether → HCID 9983249, compound

HRID 1797237Notes

Reaction equation

HRID 1797237 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C@H:12]([N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][C:24]=3[NH:28][C:29]([CH:31]3[CH2:33][CH2:32]3)=[O:30])[CH2:19]2)[CH2:13][C:14](=[O:17])[NH:15][OH:16])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[C:34](OC(=O)C)(=[O:36])[CH3:35].CCOCC.CCCCCC>C(#N)C.C(Cl)Cl>[C:34]([O:16][NH:15][C:14]([CH2:13][C@@H:12]([N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][C:24]=2[NH:28][C:29]([CH:31]2[CH2:33][CH2:32]2)=[O:30])[CH2:19]1)[C:6]1[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=1)=[O:17])(=[O:36])[CH3:35]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 7918Acetic AnhydrideHCID 8058HexaneHCID 10095424HCID 10095424, compound

Product 1

HCID 9983249HCID 9983249, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Procedure

A solution of (1R)-cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-2-hydroxycarbamoyl-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide and acetic anhydride (0.09 mL, 1 mmol) in acetonitrile/methylene chloride (6 mL each) was stirred at room temperature for 21 hrs. Ether (10 mL) and hexane (10 mL) was added to give a suspension. The suspension was filtered to give (1R)-cyclopropanecarboxylic acid {2-[2-acetoxycarbamoyl-1-(3-ethoxy-4-methoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (270 mg, 63% yield): mp, 140–142° C.; 1H NMR (DMSO-d6) δ 0.88–0.92 (m, 4H, 2CH2), 1.30 (t, J=7 Hz, 3H, CH3), 1.75–1.81 (m, 1H, CH), 2.09 (s, 3H, CH3), 3.02–3.07 (m, 2H, CH2), 3.73 (s, 3H, CH3), 4.01 (q, J=7 Hz, 2H, CH2), 4.18 (d, J=18 Hz, 1H, NCHH), 4.60 (d, J=18 Hz, 1H, NCHH), 5.67 (t, J=8 Hz, 1H, NCH), 6.86–6.95 (m, 3H, Ar), 7.18 (d, J=8 Hz, 1H, Ar) 7.49 (t, J=8 Hz, 1H, Ar), 8.23 (d, J=8 Hz, 1H, Ar), 10.54 (s, 1H, NH), 11.86 (s, 1H, NH); 13C NMR (DMSO-d6) δ 7.79, 14.70, 15.46, 17.95, 17.95, 34.55, 46.53, 51.06, 55.44, 63.76, 111.87, 111.99, 116.77, 117.29, 117.47, 119.23, 131.17, 132.74, 136.94, 142.25, 147.92, 148.52, 166.48, 168.02, 168.32, 171.70; Anal Calcd for C26H29N3O7+0.1 H2O: C, 62.79; H, 5.92; N, 8.45, H2O, 0.36. Found: C, 62.44; H, 5.82; N, 8.37, H2O, 0.30.

Workup

  1. customto give a suspension
  2. filtrationThe suspension was filtered

Sources & evidence

ORD record
ord-53f79e6ff6234453830948c8da01d261
Source dataset
uspto-grants-2006_04
Patent number
US07034052B2

Reaction notes

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