Allyltributylstannane → 4-Fluoro-2-methoxy-5-(2-propen-1-yl)benzonitrile

HRID 1519552Notes

Reaction equation

HRID 1519552 reaction equation
[F:1][C:2]1[C:9](I)=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:11][CH3:12])[CH:3]=1.[Cl-].[Li+].[CH2:15]([Sn](CCCC)(CCCC)CCCC)[CH:16]=[CH2:17]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[F:1][C:2]1[C:9]([CH2:17][CH:16]=[CH2:15])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:11][CH3:12])[CH:3]=1

Participants

6

Reactant 3

HCID 90628AllyltributylstannaneHCID 433294Lithium ChlorideHCID 67514531HCID 67514531, compound

Product 1

HCID 675133654-Fluoro-2-methoxy-5-(2-propen-1-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

To a mixture of 4-fluoro-5-iodo-2-methoxybenzonitrile (2.5 g, 9.0 mmol), Pd(Ph3P)4 (1.0 g, 0.90 mmol) and lithium chloride (0.96 g, 23 mmol) under nitrogen was added anhydrous toluene (50 mL) and the mixture was flushed (3×) with nitrogen. Allyltributyltin (4.15 mL, 14 mmol) was added and the mixture was flushed again with nitrogen. The reaction was heated under nitrogen at 115° C. for 2.5 hours and then let cool to room temperature. TLC (10% ethyl acetate/Hexanes) showed several spots with a strongly charring product spot right above the starting material. The reaction was diluted with hexanes and filtered to remove insoluble material. The mother liquor was concentrated and the residue was purified on a Biotage 65+M column with a gradient elution from 0 to 40% ethyl acetate in hexanes to afford the title product which had some residual tributylstanane by-product contaminant by NMR. 1H-NMR (500 MHz, CDCl3) δ ppm 3.327 (d, J=6.5 Hz, 2H), 3.902 (s, 3H), 5.102 (2 d, J=10.0 and 17 Hz, 2H), 5.868 (m, 1H), 6.668 (d, J=11.1 Hz, 1H), 7.390 (d, J=8.0 Hz, 1H).

Workup

  1. customthe mixture was flushed (3×) with nitrogen
  2. customthe mixture was flushed again with nitrogen
  3. temperaturelet cool to room temperature
  4. additionThe reaction was diluted with hexanes
  5. filtrationfiltered
  6. customto remove insoluble material
  7. concentrationThe mother liquor was concentrated
  8. customthe residue was purified on a Biotage 65+M column with a gradient elution from 0 to 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5210ed694f7f4045b0e6d96449863734
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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