Dimethylformamide → 1-Fluoro-5,8-dihydro-9H-5,8-methanocyclohepta[c]pyridin-9-one

HRID 272601Notes

Reaction equation

HRID 272601 reaction equation
[CH:1]1([C:6]([C:8]2[C:9]([F:15])=[N:10][CH:11]=[CH:12][C:13]=2I)=[O:7])[CH2:5][CH:4]=[CH:3][CH2:2]1.C([O-])(=O)C.[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C=O)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.CCCCCC.C(OCC)(=O)C>[F:15][C:9]1[N:10]=[CH:11][CH:12]=[C:13]2[C:8]=1[C:6](=[O:7])[CH:1]1[CH2:5][CH:4]2[CH:3]=[CH:2]1

Participants

11

Reactant 4

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 68806406(Cyclopent-3-en-1-yl)(2-fluoro-4-iodopyridin-3-yl)methanone

Product 1

HCID 598378341-Fluoro-5,8-dihydro-9H-5,8-methanocyclohepta[c]pyridin-9-one

Reagents, catalysts & solvents 6

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

Cyclopent-3-enyl-(2-fluoro-4-iodo-pyridin-3-yl)-methanone (110 mg, 0.35 mmol) as prepared above, was combined with tetrabutylammonium bromide (112 mg, 0.35 mmol), potassium acetate (102 mg, 1.04 mmol), triphenylphosphine (2 mg, 0.009 mmol) and DMF (4 ml). The reaction mixture was deoxygenated with nitrogen and then palladium acetate (2 mg, 0.008 mmol) was introduced. The reaction mixture was heated in a 100° C. oil bath for 20 min. A black precipitate was observed after 7 min. The reaction mixture was cooled to room temperature and was then added to a mixture of 1:1:1:1 ethyl acetate, hexane, brine and water. The organic layer was separated and washed with brine and then dried and evaporated. The residue (60 mg) was used directly in the next step. 1H NMR (CDCl3, 400 MHz) δ 8.15 (d, 1H, J=5 Hz), 7.03 (d, 1H, J=5 Hz), 6.65 (m, 1H), 6.19(m, 1H), 3.69 (br s, 1H), 3.51 (m, 1H), 2.68 (m, 1H), 2.63 (d, 1H, J=11 Hz); APCl MS m/z 190 (M+1)+; HRMS (m/z): (M+H)+ calc'd. for C11H8FNO2: 190.0668; found, 190.0654.

Workup

  1. customThe reaction mixture was deoxygenated with nitrogen
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe organic layer was separated
  4. washwashed with brine
  5. customdried
  6. customevaporated

Sources & evidence

ORD record
ord-e2bb3ebc037341a3891e5b3248e4f3d6
Source dataset
uspto-grants-2008_11
Patent number
US07456177B2

Reaction notes

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