1,4-Diazabicyclo(3.2.2)nonane → 2-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-benzoimidazole-1-carboxylic acid tert-butyl ester

HRID 2116711Notes

Reaction equation

HRID 2116711 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1Cl)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:18]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[NH:21][CH2:20][CH2:19]2.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[N:21]1[CH:22]2[CH2:25][CH2:26][N:18]([CH2:24][CH2:23]2)[CH2:19][CH2:20]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 3984071,4-Diazabicyclo(3.2.2)nonaneHCID 634876Binap, (A+-)-HCID 23441223tert-Butyl 2-chloro-1H-benzo[d]imidazole-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 691520292-(1,4-Diaza-bicyclo[3.2.2]non-4-yl)-benzoimidazole-1-carboxylic acid tert-butyl esterYield 34.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2-Chloro-benzoimidazole-1-carboxylic acid tert-butyl ester (333 mg, 1.32 mmol), 1,4-diazabicyclo[3.2.2]nonane (57%, 195 mg, 0.88 mmol), tri(dibenzylideneacetone)dipalladium (28 mg, 0.031 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (58 mg, 0.093 mmol), sodium tert-butoxide (208 mg, 2.17 mmol) and toluene (1.55 mL) were added to a flame dried round bottom flask purged with nitrogen. The mixture was placed in an oil bath at 80° C. for 18 h and then cooled to RT. The mixture was filtered through a pad of celite and washed with chloroform and methanol. The filtrate was concentrated and the residue was purified by chromatography (Biotage, 12M) eluting with 8% methanol in chloroform with 20 drops of NH4OH per liter of eluent to afford 104 mg (34%) of 2-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-benzoimidazole-1-carboxylic acid tert-butyl ester: MS (Cl) m/z 343.1 (M+1).

Workup

  1. customdried round bottom flask
  2. custompurged with nitrogen
  3. filtrationThe mixture was filtered through a pad of celite
  4. washwashed with chloroform and methanol
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by chromatography (Biotage, 12M)
  7. washeluting with 8% methanol in chloroform with 20 drops of NH4OH per liter of eluent

Sources & evidence

ORD record
ord-304ca51fad6c4c08a6c812d8af697faf
Source dataset
uspto-grants-2008_10
Patent number
US07439236B2

Reaction notes

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