1,2-Dichloroethane → (2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone

HRID 334939Notes

Reaction equation

HRID 334939 reaction equation
[CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.Cl.Cl.[CH2:45]1[C:53]2[C:48](=[CH:49][C:50]([C:54]3([OH:61])[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]3)=[CH:51][CH:52]=2)[CH2:47][NH:46]1.C(N(CC)CC)C>C(Cl)Cl.C1COCC1.CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11]([N:46]1[CH2:47][C:48]2[C:53](=[CH:52][CH:51]=[C:50]([C:54]3([OH:61])[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]3)[CH:49]=2)[CH2:45]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 498640162,4-Bis(benzyloxy)-5-isopropenylbenzoic acidHCID 666725264-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride

Product 1

HCID 46915491(2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanoneYield 55.2%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2,4-bis-benzyloxy-5-isopropenyl-benzoic acid (145 mg; 1.2 equiv.) in DCM (5 ml) was treated with EDC (80 mg; 1.3 equiv.) and HOAt (66 mg; 1.5 equiv.) then stirred at room temperature for 30 minutes. This solution was then added to a mixture of 4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride (112 mg; 0.32 mmol) and triethylamine (90 μl; 2 equiv.) in THF (5 ml) and DMF (2 ml), the reaction was then stirred at room temperature overnight. The reaction mixture was diluted with EtOAc, washed with water, 1N NaOH and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 5% 2M methanolic ammonia/DCM gave 104 mg of (2,4-bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone as a yellow glass.

Workup

  1. stirringthe reaction was then stirred at room temperature overnight
  2. washwashed with water, 1N NaOH and brine
  3. customthe EtOAc layer was separated
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customPurification by flash column chromatography
  7. washon SiO2, gradient elution from 0% to 5% 2M methanolic ammonia/DCM

Sources & evidence

ORD record
ord-de1cfc93050b452588bbb8f085dbdf5d
Source dataset
uspto-grants-2014_11
Patent number
US08883790B2

Reaction notes

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