Dimethyl Sulfoxide → tert-Butyl 7-[4-(4-cyanophenyl)-4-(4-pyridinylmethoxy)butyl]-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylate

HRID 991491Notes

Reaction equation

HRID 991491 reaction equation
[H-].[Na+].CS(C)=O.[C:7]([C:9]1[CH:14]=[CH:13][C:12]([CH:15]([OH:35])[CH2:16][CH2:17][CH2:18][N:19]2[CH2:26][CH:25]3[CH2:27][CH:21]([CH2:22][N:23]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24]3)[CH2:20]2)=[CH:11][CH:10]=1)#[N:8].[N:36]1[CH:41]=[CH:40][C:39]([CH2:42]Cl)=[CH:38][CH:37]=1>CN(C=O)C.O>[C:7]([C:9]1[CH:10]=[CH:11][C:12]([CH:15]([O:35][CH2:42][C:39]2[CH:40]=[CH:41][N:36]=[CH:37][CH:38]=2)[CH2:16][CH2:17][CH2:18][N:19]2[CH2:20][CH:21]3[CH2:27][CH:25]([CH2:24][N:23]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:22]3)[CH2:26]2)=[CH:13][CH:14]=1)#[N:8]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 745714-(Chloromethyl)pyridineHCID 11338532Tert-butyl 7-[4-(4-cyanophenyl)-4-hydroxybutyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate

Product 1

HCID 9935321tert-Butyl 7-[4-(4-cyanophenyl)-4-(4-pyridinylmethoxy)butyl]-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylateYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaH (0.059 g; 55% suspension in oil; 1.35 mmol) was washed with petroleum ether (fraction 40/60). 2 mL of DMSO was added. tert-Butyl 7-[4-(4-cyanophenyl)-4-hydroxybutyl]-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (see Example 1(x) above; 0.54 g; 1.05 mmol) dissolved in 10 mL of DMF was added dropwise at 0° C. After 15 minutes, 4-pyridinylmethyl chloride (0.17 g; 1.05 mmol) was added dropwise at 0° C. The mixture was stirred at 0° C. for 30 minutes, then at rt overnight. The reaction mixture was diluted with water and extracted with ethyl acetate:toluene (1:1). The organic layer was separated and washed with brine and water. Evaporation in vacuo gave 0.56 g of crude product. Purification on silica (DCM:10% MeOH) gave 0.17 g (26%) of the title compound.

Workup

  1. additionwas added dropwise at 0° C
  2. customat rt
  3. customovernight
  4. extractionextracted with ethyl acetate:toluene (1:1)
  5. customThe organic layer was separated
  6. washwashed with brine and water
  7. customEvaporation in vacuo
  8. customgave 0.56 g of crude product
  9. customPurification on silica (DCM:10% MeOH)

Sources & evidence

ORD record
ord-07b2a433343d4380bb341ca3e1caf8e9
Source dataset
uspto-grants-2002_10
Patent number
US06465481B1

Reaction notes

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