1-Propanol → 3-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethenylbenzonitrile

HRID 1874888Notes

Reaction equation

HRID 1874888 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](O)[CH2:22]C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[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]([CH:21]=[CH2:22])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 10311-PropanolHCID 68485937HCID 68485937, compound

Product 1

HCID 684888433-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethenylbenzonitrileYield 87%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
120 °C

Procedure

3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.70 g, 1.969 mmol) was combined with potassium vinyl trifluoroborate (0.396 g, 2.95 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (1:1) (0.058 g, 0.079 mmol) and TEA (0.412 mL, 2.95 mmol) in n-propanol (10 mL) and heated in a microwave reactor at 120° C. for 30 min. The reaction mixture was filtered through Celite™ and concentrated to dryness. The residue was dissolved in DCM, washed with saturated aqueous NaHCO3, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified on silica gel (eluted with 0 to 10% CH3OH/DCM) to give 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethenylbenzonitrile (0.52 g, 1.718 mmol, 87% yield) as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.79 (s, 1H), 7.45-7.55 (m, 2H), 7.40 (s, 1H), 7.25 (s, 1H), 6.75 (dd, 1H), 6.04 (d, 1H), 5.43 (d, 1H), 3.77 (s, 2H), 2.05 (br. s., 2H). LC-MS (ES+) m/z 303.32, 305.30 [M+H].

Workup

  1. filtrationThe reaction mixture was filtered through Celite™
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in DCM
  4. washwashed with saturated aqueous NaHCO3
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified on silica gel (eluted with 0 to 10% CH3OH/DCM)

Sources & evidence

ORD record
ord-cdb6107df69d4c32844d7d76daa0f60e
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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