HCID 178523771, compound → HCID 178519307, compound

HRID 1373039Notes

Reaction equation

HRID 1373039 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]([N:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH2:29][OH:30])[CH:26]=3)[CH2:21]2)=[O:19])[CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[O-2].[O-2].[Mn+4].C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]([N:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH:29]=[O:30])[CH:26]=3)[CH2:21]2)=[O:19])[CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 178523771HCID 178523771, compound

Product 1

HCID 178519307HCID 178519307, compound

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 6212ChloroformSolvent

Procedure

20 g of manganese dioxide was added to 120 ml of a chloroform solution containing 4.0 g of N-benzyloxycarbonyl-trans-4-[(5-hydroxymethyl-2-isoindolinyl)carbonyl]cyclohexylamine, and the mixture was stirred at room temperature for 4 hours. Manganese dioxide was removed by filtration through Celite and the solvent was removed under reduced pressure. The residue was suspended in hexane-ethyl acetate and the crystals were collected by filtration to obtain N-benzyloxycarbonyl-trans-4-[(5-formyl-2-isoindolinyl)carbonyl]cyclohexylamine. (2) To an aqueous solution containing 3.35 g of silver nitrate were added 2.75 g of the compound obtained in the above (1) and 110 ml of ethanol under ice-cooling, and then, an aqueous solution containing 2.61 g of potassium hydroxide was added dropwise thereto. The mixture was stirred under ice-cooling for 1 hour and separated by filtration through Celite, and then, the solvent was removed under reduced pressure. To the residue was added 50 ml of an aqueous 1N hydrochloric acid solution and the mixture was extracted with chloroform. After the extract was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The residue was suspended in hexane-ether and the crystals were collected by filtration to obtain N-benzyloxycarbonyl-trans-4-[(5-carboxy-2-isoindolinyl)carbonyl]cyclohexylamine. (3) The compound obtained in the above (2) was used and condensed with a starting amine compound in the same manner as in Reference Example 11-1, and subsequently treated with palladium-carbon under hydrogen atmosphere to obtain trans-4-[(5-dimethylaminocarbonyl-2-isoindolinyl)carbonyl]cyclohexylamine (Reference 13-25 in Table 8).

Workup

  1. customManganese dioxide was removed by filtration through Celite
  2. customthe solvent was removed under reduced pressure
  3. filtrationthe crystals were collected by filtration

Sources & evidence

ORD record
ord-945b16d7a6d44a8994887ab89ea3df54
Source dataset
uspto-grants-2007_01
Patent number
US07160877B2

Reaction notes

Loading…