Hydrochloric Acid → 7-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one

HRID 1947815Notes

Reaction equation

HRID 1947815 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]2[CH2:22][CH2:21][C:16]3(OCC[O:17]3)[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2.Cl>C1COCC1.O.[OH-].[Na+]>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]2[CH2:22][CH2:21][C:16](=[O:17])[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 672557217-amino-4-(1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 672561257-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 7-amino-4-(1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (1.64 g, 5.42 mmol) in THF (60 mL) was added aqueous 3.0 M HCl (1.81 mL), the resulting mixture was stirred at rt overnight. The mixture to 0° C., diluted with water and basified to pH ˜10 with 1M NaOH. The aqueous mixture was extracted with EtOAc (3×) and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 7.11 (d, J=8.34 Hz, 1H), 6.53 (d, J=8.34 Hz, 1H), 5.88 (s, 2H), 4.41 (s, 2H), 3.00 (s, 3H), 2.56 (dt, J=6.06, 14.15 Hz, 2H), 2.21-2.30 (m, 2H), 1.96-2.04 (m, 2H), 1.78-1.91 (m, 2H); MS (ES+): m/z: 260.1517 [MH+]. HPLC: tR=1.06 min (UPLC TOF MS: polar—3 min).

Workup

  1. extractionThe aqueous mixture was extracted with EtOAc (3×)
  2. washthe combined organic fractions were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-b0862ea211a3449fa60f07216b404483
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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