Methanol → 4-Amino-2-chloro-3-fluorophenol

HRID 2279047Notes

Reaction equation

HRID 2279047 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([N+:9]([O-])=O)[CH:5]=[CH:4][C:3]=1[OH:12].CO.[NH4+].[Cl-]>[Zn].C1COCC1>[NH2:9][C:6]1[CH:5]=[CH:4][C:3]([OH:12])=[C:2]([Cl:1])[C:7]=1[F:8]

Participants

6

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 702152852-Chloro-3-fluoro-4-nitrophenol

Product 1

HCID 231052224-Amino-2-chloro-3-fluorophenolYield 76%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A 0° C. solution of 2-chloro-3-fluoro-4-nitrophenol (25 g, 130.9 mmol) in 1:1 MeOH and THF (400 mL) was treated with NH4Cl (70 g, 1.3 mol), followed by the portion-wise addition of zinc (83.2 g, 1.3 mol), then warmed to RT and stirred for 2 h. The solids were removed via filtration, the filtrate concentrated to dryness and the residue was dissolved in EtOAc, washed with brine, dried over Na2SO4 and concentrated to afford 4-amino-2-chloro-3-fluorophenol (16 g, 76%). 1H-NMR (400 MHz, DMSO-d6): δ 9.41 (s, 1 H), 6.59-6.51 (m, 2 H), 4.65 (s, 2H); MS (ESI): m/z 162.2 [M+H]+.

Workup

  1. customThe solids were removed via filtration
  2. concentrationthe filtrate concentrated to dryness
  3. dissolutionthe residue was dissolved in EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3693b357cfe449a7a87b63ddde25037c
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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