8-Methyl-8-azabicyclo(3.2.1)octan-3-ol → HCID 22562209, compound

HRID 982634Notes

Reaction equation

HRID 982634 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH:8]2[CH2:9][CH:10]([OH:12])[CH2:11][CH:5]1[CH2:6][CH2:7]2.Cl[C:14]1[N:18]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]3([CH3:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:21][CH2:20]2)[C:17]2[CH:34]=[CH:35][CH:36]=[CH:37][C:16]=2[N:15]=1>CN(C=O)C>[CH3:3][N:4]1[CH:8]2[CH2:7][CH2:6][CH:5]1[CH2:11][CH:10]([O:12][C:14]1[N:18]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]4([CH3:33])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)[CH2:21][CH2:20]3)[C:17]3[CH:34]=[CH:35][CH:36]=[CH:37][C:16]=3[N:15]=1)[CH2:9]2

Participants

5

Reactant 3

HCID 84248-Methyl-8-azabicyclo(3.2.1)octan-3-olHCID 24758Sodium hydrideHCID 22562192HCID 22562192, compound

Product 1

HCID 22562209HCID 22562209, compoundYield 20.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of NaH (60% oil suspension, 102.8 mg, 2.57 mmol was used after washing with n-hexane) in DMF (1.5 ml) was added a solution of tropine (190.6 mg, 1.35 mmol) in DMF (1.5 ml) dropwise at 0° C. After 0.5 hour stirring, a solution of 2-chloro-1-[1-(1-methylcyclooctyl)-4-piperidinyl]-1H-benzimidazole (162 mg, 0.45 mmol) in DMF (3 ml) was added to the reaction mixture at 0° C. The resulting mixture was stirred at room temperature for 23 hours and then at 120° C. for 19 hours. After cooling down to 0° C., the reaction mixture was quenched with water and extracted with CH2Cl2. The extracts combined were washed with brine, dried (Na2SO4), filtered, and concentrated to give 391.1 mg of crude oil, which was purified by preparative TLC (1 mm thick plate×3, CH2Cl2/MeOH:10/1) to afford 42.3 mg (20%) of title compound as a brown oil.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 23 hours
  2. waitat 120° C. for 19 hours
  3. customthe reaction mixture was quenched with water
  4. extractionextracted with CH2Cl2
  5. washThe extracts combined were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give 391.1 mg of crude oil, which
  10. customwas purified by preparative TLC (1 mm thick plate×3, CH2Cl2/MeOH:10/1)

Sources & evidence

ORD record
ord-1b98060df97c410da0e50432e0a749e8
Source dataset
uspto-grants-2005_03
Patent number
US06861425B2

Reaction notes

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