Dimethylformamide → HCID 86690343, compound

HRID 2409894Notes

Reaction equation

HRID 2409894 reaction equation
[C@H:1]12[CH2:8][C@H:4]([CH2:5][CH:6]1[OH:7])[CH2:3][NH:2]2.F[C:10]1[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=1.CN(C=O)C.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O>[OH:7][CH:6]1[C@H:1]2[CH2:8][C@H:4]([CH2:3][N:2]2[C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[CH2:5]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 145174-FluorobenzonitrileHCID 86690344HCID 86690344, compound

Product 1

HCID 86690343HCID 86690343, compoundYield 47.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a round bottom flask was added (1S,4R)-2-azabicyclo[2.2.1]heptan-6-ol (0.5 gm, 3.34 mmol), 4-fluorobenzonitrile (0.405 gm, 3.34 mmol), DMF (6 ml) and K2CO3 (1.386 gm, 10.03 mmol). The reaction was stirred at 80° C. for 5 hrs. After this time, the reaction was diluted with EtOAc. The resulting solution was washed with water (4×) and saturated aqueous NaCl. The organic layer was separated, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give product 4-((1R,4S)-6-hydroxy-2-azabicyclo[2.2.1]heptan-2-yl)benzonitrile (338 mg, 1.578 mmol, 47.2% yield) as a white solid. Anal. Calcd. for C13H14N2O m/z 214.2, found: 215.1 (M+H)+.

Workup

  1. washThe resulting solution was washed with water (4×) and saturated aqueous NaCl
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified
  7. washeluting with a gradient of 0-100% EtOAc/Hex

Sources & evidence

ORD record
ord-74e302319c6f4c3380158a407c2416db
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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