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

반응식

HRID 41440 반응식
[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

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f91182f52bc8487dba5ae67f09c2c791
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530469B2

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