Ammonium Chloride → 2-(4-Amino-3-methylphenoxy)-5-fluorobenzonitrile

HRID 1897447Notes

Reaction equation

HRID 1897447 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[C:13]([CH3:20])[CH:12]=2)=[C:6]([CH:9]=1)[C:7]#[N:8].[NH4+].[Cl-]>[Zn].CO.C1COCC1>[NH2:17][C:14]1[CH:15]=[CH:16][C:11]([O:10][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:9][C:6]=2[C:7]#[N:8])=[CH:12][C:13]=1[CH3:20]

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 574187545-Fluoro-2-(3-methyl-4-nitrophenoxy)-benzonitrile

Product 1

HCID 574187552-(4-Amino-3-methylphenoxy)-5-fluorobenzonitrile

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

Intermediate (24t) (14.3 g, mmol) and zinc dust (17.2 g, 263 mmol) were suspended in mixed solvent of MeOH/THF (1:1, 125 mL) and saturated NH4Cl (125 mL) was added. The reaction mixture became warm. There was an obvious change in the zinc suspension. The reaction was finished in 10 minutes. The reaction mixture was filtered through a silica plug and diluted with EtOAc and saturated NaHCO3. The layers were separated and the combined organics dried over MgSO4 and concentrated under reduced pressure. The crude residue (25t) was pure enough on NMR spectra. 1H NMR (400 MHz, d6-DMSO) δ 7.83 (dd, J=8.5, 3.1 Hz, 1H), 7.47 (td, J=8.9, 3.1 Hz, 1H), 6.83-6.77 (m, 2H), 6.74 (dd, J=8.6, 2.3 Hz, 1H), 6.66 (d, J=8.6 Hz, 1H), 4.88 (s, 1H), 2.06 (s, 3H) ppm.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture became warm
  3. filtrationThe reaction mixture was filtered through a silica plug
  4. additiondiluted with EtOAc and saturated NaHCO3
  5. customThe layers were separated
  6. dry with materialthe combined organics dried over MgSO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-84fe86de6ec747bfbc97a12f51065714
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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