1,2-Dichloroethane → HCID 9907165, compound

HRID 2303326Notes

Reaction equation

HRID 2303326 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][CH:7]2[CH2:13][CH:12]3[NH:14][CH:9]([CH2:10][CH2:11]3)[CH2:8]2)=[CH:4][CH:3]=1.C[Si](C)(C)CCOC[N:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=[C:24]1[CH:32]=O.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]2[CH2:13][CH:12]3[N:14]([CH2:32][C:24]4[NH:25][C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=5[N:23]=4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 120171281-(2-Trimethylsilylethoxymethyl)-2-formyl-benzimidazoleHCID 18461101HCID 18461101, compound

Product 1

HCID 9907165HCID 9907165, compoundYield 113.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of 0.5 g of 3-(4-chloro-benzyl)-8-aza-bicyclo[3.2.1]octane, 0.5 g of 1-(2-trimethylsilylethoxymethyl)-1H-benzimidazole-2-carbaldehyde, 5 mL of 1,2-dichloroethane and 0.5 g of sodium triacetoxyborohydride was stirred at room temperature for 48 h. The reaction mixture was diluted with 50 mL chloroform and 10 mL saturated aqueous Na2CO3 and the layers separated. The aqueous layer was extracted with 2×25 mL of chloroform and the combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The crude SEM ether was heated to reflux in 50 mL of ethanol containing 5 mL of 3N HCl for 2 h, cooled, concentrated and partitioned between 10 ml of saturated aqueous Na2CO3 and 3×25 mL of chloroform. The chloroform extracts were dried over MgSO4 and concentrated. Purification by chromatography eluting with 90:10 CHCl3:MeOH gave 0.75 g of 2-[3-(4-chloro-benzyl)-8-aza-bicyclo[3.2.1]oct-8-ylmethyl]-1H-benzimidazole as a 2:1 mixture of exo:endo isomers. Chromatography on a Chiralpak™ AS column eluting with a 90:10 mixture of hexane with 0.10% diethylamine and isopropanol gave 0.25 g of endo 2-[3-(4-chloro-benzyl)-8-aza-bicyclo[3.2.1]oct-8-ylmethyl]-1H-benzimidazole: RT=5.34 min; MS (m+1)=366; 1H NMR (400 MHz, CDCl3 3.8 (s, 2H), 3.2 (s, 2H), 2.75 (d, 2H), 2.05 (m, 2H), 1.8 (d, 2H).

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with 2×25 mL of chloroform
  3. dry with materialthe combined organic layers were dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. temperatureThe crude SEM ether was heated
  6. temperatureto reflux in 50 mL of ethanol containing 5 mL of 3N HCl for 2 h
  7. temperaturecooled
  8. concentrationconcentrated
  9. custompartitioned between 10 ml of saturated aqueous Na2CO3 and 3×25 mL of chloroform
  10. dry with materialThe chloroform extracts were dried over MgSO4
  11. concentrationconcentrated
  12. customPurification by chromatography
  13. washeluting with 90:10 CHCl3

Sources & evidence

ORD record
ord-f53f4c750fba49119d6a3dca3cf2df16
Source dataset
uspto-grants-2002_08
Patent number
US06432976B1

Reaction notes

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