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

HRID 1875081Notes

Reaction equation

HRID 1875081 reaction equation
[Br:1][C:2]1[C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:14]=[C:15]([Cl:17])[CH:16]=2)[C:12]#[N:13])=[C:6]([F:18])[C:5]([CH2:19]Br)=[CH:4][CH:3]=1.[NH3:21].CO>O1CCCC1>[NH2:21][CH2:19][C:5]1[C:6]([F:18])=[C:7]([O:8][C:9]2[CH:10]=[C:11]([CH:14]=[C:15]([Cl:17])[CH:16]=2)[C:12]#[N:13])[C:2]([Br:1])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 669997373-(6-Bromo-3-bromomethyl-2-fluoro-phenoxy)-5-chloro-benzonitrile

Product 1

HCID 671971663-{[3-(Aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrileYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-{[6-bromo-3-(bromomethyl)-2-fluorophenyl]oxy}-5-chlorobenzonitrile (2.5 g, 5.96 mmol) in tetrahydrofuran (THF) (50 mL) was added dropwise to a 7M solution of ammonia in MeOH (42.6 mL, 298 mmol) at RT under nitrogen. The reaction was stirred for 16 h then the reaction mixture was evaporated to dryness. Ethyl acetate and saturated aqueous sodium bicarbonate were added to the residue and the mixture was shaken in a separatory funnel. The organic layer was dried over sodium sulfate and the solvent was evaporated. The residue was purified by chromatography with hexane:ethyl acetate to give the title compound (0.453 g, 21%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.76 (s, 1H), 7.56 (d, 1H), 7.39-7.46 (m, 2H), 7.37 (m, 1H), 3.70 (s, 2H), 1.85 (br. s., 2H).

Workup

  1. customthe reaction mixture was evaporated to dryness
  2. additionEthyl acetate and saturated aqueous sodium bicarbonate were added to the residue
  3. stirringthe mixture was shaken in a separatory funnel
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customthe solvent was evaporated
  6. customThe residue was purified by chromatography with hexane

Sources & evidence

ORD record
ord-43280d3f376c45f88f54bd8e5bf93c32
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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