Sodium Carbonate → Ethyl 7-(3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate

HRID 597980Notes

Reaction equation

HRID 597980 reaction equation
FC(F)(F)S(O[C:7]1[CH2:14][CH:13]2[CH2:15][CH:9]([CH2:10][N:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12]2)[CH:8]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+].[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O>C(COC)OC.CCOCC>[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:7]2[CH2:14][CH:13]3[CH2:15][CH:9]([CH2:10][N:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12]3)[CH:8]=2)[CH:32]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 2762745Pyridine-2-boronic acidHCID 57486348Ethyl 7-(trifluoromethylsulfonyloxy)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate

Product 1

HCID 57485784Ethyl 7-(3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylateYield 33%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of ethyl 7-(trifluoromethylsulfonyloxy)-3-azabicyclo[3.3.1]non-6-ene-3-carboxylate (0.34 g, 1.0 mmol) in dimethoxyethane (8 ml) was added saturated sodium carbonate solution (2.5 ml), lithium chloride (127 mg, 3.0 mmol) and pyridinylboronic acid (123 mg, 1.00 mmol). The flask was alternately evacuated and filled with argon three times. Then palladium tetrakistriphenylphosphine (23 mg, 0.02 mmol) was added and the evacuate/fill procedure performed once again. The flask was then sealed under argon and the stirred reaction mixture was heated at 95° C. for 2 h. The mixture was cooled to room temperature and then diluted with ether (10 ml) and filtered through a Celite pad. The Celite was washed with 30% ammonium hydroxide (25 ml) and ether (50 ml). The combined filtrates were separated into organic and aqueous phases, and the aqueous layer was extracted with ether (1×25 ml). Chloroform (20 ml) was added to the combined organic layers, and the mixture was dried over sodium sulfate and filtered. Concentrated of the filtrate by rotary evaporation, followed by purification of the residue (207 mg) by column chromatography, using a gradient of chloroform/methanol (0 to 2% methanol) as eluent, gave a light yellow oil (90 mg, 33%).

Workup

  1. customThe flask was alternately evacuated
  2. additionfilled with argon three times
  3. customThe flask was then sealed under argon
  4. customthe stirred reaction mixture
  5. temperatureThe mixture was cooled to room temperature
  6. filtrationfiltered through a Celite pad
  7. washThe Celite was washed with 30% ammonium hydroxide (25 ml) and ether (50 ml)
  8. customThe combined filtrates were separated into organic and aqueous phases
  9. extractionthe aqueous layer was extracted with ether (1×25 ml)
  10. additionChloroform (20 ml) was added to the combined organic layers
  11. dry with materialthe mixture was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationConcentrated of the filtrate by rotary evaporation
  14. customfollowed by purification of the residue (207 mg) by column chromatography

Sources & evidence

ORD record
ord-8c52f259dc0f4f4f9778b55104db6f41
Source dataset
uspto-grants-2011_03
Patent number
US07897611B2

Reaction notes

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