Acrylonitrile → (1R*,5S*,6R*)-8-Benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]oct-3-ene-2-one

HRID 2088113Notes

Reaction equation

HRID 2088113 reaction equation
[Br-].[CH2:2]([N+:9]1[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[C:10]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:22](#[N:25])[CH:23]=[CH2:24].C(N(CC)CC)C>O1CCOCC1>[CH2:2]([N:9]1[C@@H:14]2[C@H:23]([C:22]#[N:25])[CH2:24][C@@:10]1([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:11](=[O:15])[CH:12]=[CH:13]2)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 7855AcrylonitrileHCID 8471TriethylamineHCID 21931695N-benzyl-3-hydroxy-2-phenylpyridinium bromide

Product 1

HCID 69684828(1R*,5S*,6R*)-8-Benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]oct-3-ene-2-oneYield 24%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

N-benzyl-3-hydroxy-2-phenylpyridinium bromide (20 g, 58.3 mmol), acrylonitrile (50 ml, 755 mmol) and triethylamine (20 ml, 143 mmol) were mixed and stirred at reflux for 20 hours in 1,4-dioxane (150 ml). The mixture was partitioned between saturated sodium hydrogen carbonate and ethyl acetate. The organic layer was separated, dried (MgSO4), filtered and concentrated. The residue was chromatographed on silica gel eluting with 25, 35 and 45% diethyl ether/iso-hexanes to yield the title compound (4.4 g, 24%).

Workup

  1. customThe mixture was partitioned between saturated sodium hydrogen carbonate and ethyl acetate
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel eluting with 25, 35 and 45% diethyl ether/iso-hexanes

Sources & evidence

ORD record
ord-a057ac815af04a80bb2b335d0d7f6433
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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