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

HRID 1596518ノート

反応式

HRID 1596518 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6212Chloroform溶媒

実験手順

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-hydroxybicyclo[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-dichloroethane 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).

後処理

  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

出典と根拠

ORDレコード
ord-822aad3b2cb74122a922911996a0656d
出典データセット
uspto-grants-2001_09
特許番号
US06291499B1

反応ノート

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