4-Vinylpyridine → (R)-(-)-5'-(2-(4-Pyridyl)ethenyl)spiro[1-azabicyclo[2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine]

HRID 49613

Reaction equation

HRID 49613 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH2:10][C@:9]3([CH:15]4[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]4)[CH2:11]3)[O:8][C:5]2=[N:6][CH:7]=1.[CH:18]([C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)=[CH2:19].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:23]1[CH:24]=[CH:25][C:20]([CH:18]=[CH:19][C:2]2[CH:3]=[C:4]3[CH2:10][C@:9]4([CH:15]5[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]5)[CH2:11]4)[O:8][C:5]3=[N:6][CH:7]=2)=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 75024-VinylpyridineHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 54506690(2R)-5'-bromo-3'H-spiro[4-azabicyclo[2.2.2]octane-2,2'-furo[2,3-b]pyridine]

Product 1

HCID 53757590(R)-(-)-5'-(2-(4-Pyridyl)ethenyl)spiro[1-azabicyclo[2.2.2]octane-3,2'(3'H)-furo[2,3-b]pyridine]Yield 72%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
102.5 °C

Procedure

(R)-(−)-5′-Bromospiro[1-azabicyclo[2.2.2]octane-3,2′(3′H)-furo[2,3-b]pyridine] (295 mg, 1 mmol), 4-vinylpyridine (0.135 mL, 1.25 mmol), palladium(II)acetate (7.2 mg, 0.032 mmol), tri-o-tolylphosphine (38.7 mg, 0.127 mmol), and triethylamine (0.5 mL, 3.6 mmol) in anhydrous acetonitrile (0.5 mL) were combined in a heavy-walled threaded glass tube containing a magnetic stir bar, purged with argon and sealed with a Teflon plug and FETFE O-ring. The mixture was stirred and heated at 100 to 105° C. for 48 hours, cooled to room temperature, dissolved in chloroform (25 mL), washed with saturated aqueous sodium carbonate (2 mL), dried (MgSO4), and evaporated under reduced pressure. Purification by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5), followed by recrystallization from acetone afforded the title compound (230 mg, 0.72 mmol, 72%): electrospray MS (m/z, relative intensity) 320 ([MH]+, 100).

Workup

  1. additioncontaining a magnetic stir bar
  2. custompurged with argon
  3. customsealed with a Teflon plug and FETFE O-ring
  4. temperaturecooled to room temperature
  5. dissolutiondissolved in chloroform (25 mL)
  6. washwashed with saturated aqueous sodium carbonate (2 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated under reduced pressure
  9. customPurification by flash chromatography through silica gel (eluting with ammoniated chloroform/methanol, 95:5)
  10. customfollowed by recrystallization from acetone

Sources & evidence

ORD record
ord-34ce5c0d9f7c4dfd97e2ec1e88b787b9
Source dataset
uspto-grants-2004_03
Patent number
US06706878B2

Linked notes

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