Sodium Acetate → (1H-benzimidazol-2-ylmethyl)-[5-(4-chloro-benzyl)-bicyclo[2.2.2]oct-2-yl]-amine

HRID 843676Notizen

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[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][CH:7]2[CH2:12][CH:11]3[CH2:13][CH2:14][CH:8]2[CH2:9][CH:10]3O)=[CH:4][CH:3]=1.Cl.Cl.[NH2:20][CH2:21][C:22]1[NH:23][C:24]2[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=2[N:26]=1.C([O-])(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.ClCCCl>[NH:23]1[C:24]2[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=2[N:26]=[C:22]1[CH2:21][NH:20][CH:10]1[CH2:9][CH:8]2[CH2:14][CH2:13][CH:11]1[CH2:12][CH:7]2[CH2:6][C:5]1[CH:16]=[CH:17][C:2]([Cl:1])=[CH:3][CH:4]=1

Komponenten

7

Edukt 4

HCID 517045Sodium AcetateHCID 2723957(1H-benzo[d]imidazol-2-yl)methanamine dihydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 183789955-(4-Chloro-benzyl)-bicyclo[2.2.2]octan-2-ol

Produkt 1

HCID 9821201(1H-benzimidazol-2-ylmethyl)-[5-(4-chloro-benzyl)-bicyclo[2.2.2]oct-2-yl]-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 6212ChloroformLösungsmittel

Versuchsvorschrift

Example 6 was prepared in a similar manner to Examples 4 and 5 above. A mixture of 250 mg of 3:1 mixture of exo and endo 5-(4-chloro-benzyl)-bicyclo[2.2.2]octan-2-one was prepared from 5-acetoxy-5-cyanobicyclo[2.2.2]octan-2-one in three sequential steps without isolating intermediate products. The first two steps were similar to those described in Steps 1 and 2 of Example 4 above, sequential treatment with sodium borohydride in ethanol, sodium hydroxide, formed 5-hydroxy-bicyclo[2.2.2]octan-2-one. Olefination, hydrogenation, and Swern oxidation of the product, 5-(4-chloro-benzyl)-bicyclo[2.2.2]octan-2-ol followed. To the resulting product was added 400 mg of 2-aminomethylbenzimidazole dihydrochloride, 150 mg of anhydrous sodium acetate, 10 mL of 1,2-dichloroetharie and 400 mg of sodium triacetoxyborohydride, and stirred overnight in a stoppered flask. The mixture was diluted with 50 mL of chloroform and washed with 20 mL of saturated sodium carbonate. The organic extract was dried over magnesium sulfate and concentrated under reduced pressure. Preparative TLC eluting with 95:5:5 ethyl acetate:methanol:triethyl amine gave (1H-benzimidazol-2-ylmethyl)-[5-(4-chloro-benzyl)-bicyclo[2.2.2]oct-2-yl]-amine as a racemic mixture of four diastereomers: MS (m+1)=380.9; 1H NMR (400 MHz, CDCl3) 7.6 (br s, 1H), 7.2 (m, 4H), 7.05 (m, 2H), 4.04 and 4.06 (2×s, 2H), 2.85 (m, 1H), 2.6-5 (m, 3H), 2.0-1.0 (complex, 12H).

Aufarbeitung

  1. washwashed with 20 mL of saturated sodium carbonate
  2. extractionThe organic extract
  3. dry with materialwas dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. washPreparative TLC eluting with 95:5:5 ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-dd8e5c1a3f704b4ea9b92624a46c3dd1
Quelldatensatz
uspto-grants-2002_04
Patentnummer
US06380205B1

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