Ammonia → 3-{[3-(Aminomethyl)-2,6-difluorophenyl]oxy}-5-chlorobenzonitrile

HRID 1875097Notes

Reaction equation

HRID 1875097 reaction equation
[NH3:1].CO.Br[CH2:5][C:6]1[C:7]([F:23])=[C:8]([O:13][C:14]2[CH:15]=[C:16]([CH:19]=[C:20]([Cl:22])[CH:21]=2)[C:17]#[N:18])[C:9]([F:12])=[CH:10][CH:11]=1>C1COCC1>[NH2:1][CH2:5][C:6]1[C:7]([F:23])=[C:8]([O:13][C:14]2[CH:15]=[C:16]([CH:19]=[C:20]([Cl:22])[CH:21]=2)[C:17]#[N:18])[C:9]([F:12])=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 684853683-{[3-(Bromomethyl)-2,6-difluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 684855473-{[3-(Aminomethyl)-2,6-difluorophenyl]oxy}-5-chlorobenzonitrileYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 7M solution of ammonia in MeOH (45.8 mL, 321 mmol) was added to a solution of 3-{[3-(bromomethyl)-2,6-difluorophenyl]oxy}-5-chlorobenzonitrile (2.3 g, 6.41 mmol) in THF (30 mL) at RT. The reaction was capped and stirred for 16 h at RT then concentrated to dryness under vacuum. Ethyl acetate (200 mL) and saturated aqueous NaHCO3 solution (300 mL) were added. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (2×200 mL), water (200 mL), brine (200 mL), dried over Na2SO4, filtered and concentrated to give a white solid. The crude product was purified on silica gel (10% MeOH/DCM) to give the title compound (1.63 g, 86%) as a white solid (N4011-13-100). 1H NMR (400 MHz, DMSO-d5) δ ppm 7.82 (s, 1H), 7.40-7.66 (m, 3H), 7.31 (t, 1H), 3.75 (s, 2H), 1.86 (br. s., 2H).

Workup

  1. customThe reaction was capped
  2. concentrationthen concentrated to dryness under vacuum
  3. additionEthyl acetate (200 mL) and saturated aqueous NaHCO3 solution (300 mL) were added
  4. customThe organic layer was separated
  5. washwashed with saturated aqueous NaHCO3 solution (2×200 mL), water (200 mL), brine (200 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a white solid
  10. customThe crude product was purified on silica gel (10% MeOH/DCM)

Sources & evidence

ORD record
ord-77064fd2031f46eb892b06beb08e3c49
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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