Potassium (prop-1-en-2-yl)trifluoroborate → 3-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(1-methylethenyl)benzonitrile

HRID 1874928Notes

Reaction equation

HRID 1874928 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.[C:21]([B-](F)(F)F)([CH3:23])=[CH2:22].[K+]>C(O)CC>[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]([C:21]([CH3:23])=[CH2:22])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 23670158Potassium (prop-1-en-2-yl)trifluoroborate2×HCID 68485937HCID 68485937, compound

Product 1

HCID 684871183-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(1-methylethenyl)benzonitrileYield 38.3%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
120 °C

Procedure

3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-bromobenzonitrile (0.41 g, 1.153 mmol) was combined with potassium isopropenyltrifluoroborate (0.189 g, 1.268 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) dichloromethane complex (0.034 g, 0.046 mmol) and TEA (0.241 mL, 1.730 mmol) in n-propanol (10 mL) and heated in a microwave reactor at 120° C. for 90 min. Additional potassium isopropenyltrifluoroborate (0.086 g, 0.577 mmol) was added to the reaction mixture which was heated in a microwave reactor at 120° C. for an additional 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 40 g silica gel eluted with 0 to 10% CH3OH/DCM to give 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(1-methylethenyl)benzonitrile (0.140 g, 0.442 mmol, 38.3% yield) as a brown oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.74 (s, 1H), 7.46-7.54 (m, 2 H), 7.43 (s, 1H), 7.21 (s, 1H), 5.57 (s, 1H), 5.25 (s, 1H), 3.77 (s, 2H), 2.10 (s, 3H), 1.99 (br. s., 2H). LC-MS (ES+) m/z 317.19, 319.17 [M+H].

Workup

  1. temperaturewas heated in a microwave reactor at 120° C. for an additional 30 min
  2. filtrationThe reaction mixture was filtered through celite and
  3. concentrationconcentrated to dryness
  4. dissolutionThe residue was dissolved in DCM
  5. washwashed with saturated aqueous NaHCO3
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude material was purified on 40 g silica gel
  10. washeluted with 0 to 10% CH3OH/DCM

Sources & evidence

ORD record
ord-9f50ba75ff114548980dd44dc7a0f27c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…