Allyltributylstannane → 3-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(2-propen-1-yl)benzonitrile

HRID 1874923Notes

Reaction equation

HRID 1874923 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17](Br)[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[CH2:21]([Sn](CCCC)(CCCC)CCCC)[CH:22]=[CH2:23]>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([CH2:23][CH:22]=[CH2:21])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1

Participants

5

Reactant 2

HCID 90628AllyltributylstannaneHCID 68485937HCID 68485937, compound

Product 1

HCID 684835313-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(2-propen-1-yl)benzonitrileYield 54.3%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.300 g, 0.844 mmol), allyltributyl tin (0.414 mL, 1.350 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.097 g, 0.084 mmol) were combined in DMF (7 mL), purged with nitrogen, and heated at 160° C. in a microwave reactor for 30 min. The reaction mixture was filtered through Celite, diluted with EtOAc, and washed four times with dilute aqueous NaHCO3. The organic phase was isolated, dried over MgSO4, filtered and concentrated to dryness. The residue was purified on 40 g silica gel eluted successively with EtOAc followed by 0 to 10% CH3OH/DCM to give 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(2-propen-1-yl)benzonitrile (0.145 g, 0.458 mmol, 54.3% yield) as a clear oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.45-7.53 (m, 2H), 7.42 (s, 1H), 7.22 (s, 1H), 7.13 (s, 1H), 5.87-6.00 (m, 1H), 5.04-5.14 (m, 2H), 3.76 (s, 2H), 3.41 (d, J=6.59 Hz, 2H), 2.18-2.46 (br. s., 2H). LC-MS (ES−) m/z 315.20, 317.08 [M−1]. LC-MS (ES+) m/z 317.31, 319.31 [M+H].

Workup

  1. custompurged with nitrogen
  2. filtrationThe reaction mixture was filtered through Celite
  3. additiondiluted with EtOAc
  4. washwashed four times with dilute aqueous NaHCO3
  5. customThe organic phase was isolated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified on 40 g silica gel
  10. washeluted successively with EtOAc

Sources & evidence

ORD record
ord-66ed229b95e842b387e233dc50e98d67
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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