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 41440

Reaktionsgleichung

Reaktionsgleichung von HRID 41440
[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

Komponenten

10

Edukt 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

Produkt 1

HCID 46915491(2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanoneAusbeute 55,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-f91182f52bc8487dba5ae67f09c2c791
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530469B2

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