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

HRID 843676Notes

Reaction equation

HRID 843676 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6212ChloroformSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-dd8e5c1a3f704b4ea9b92624a46c3dd1
Source dataset
uspto-grants-2002_04
Patent number
US06380205B1

Reaction notes

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