Ethyl Acetate → 4-[(4-Fluorophenyl)sulfanyl]aniline

HRID 510150

Reaction equation

HRID 510150 reaction equation
[Cl-].[NH4+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][CH:12]=2)=[CH:6][CH:5]=1.C(OCC)(=O)C>O.CO.O1CCCC1.[Fe]>[F:3][C:4]1[CH:9]=[CH:8][C:7]([S:10][C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)=[CH:6][CH:5]=1

Participants

8

Reactant 3

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 27830591-Fluoro-4-[(4-nitrophenyl)sulfanyl]benzene

Product 1

HCID 27747404-[(4-Fluorophenyl)sulfanyl]anilineYield 85%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of ammonium chloride (16.63 g, 311 mmol) in water (300 mL) are added iron (17.39 g, 311 mmol) and a solution of 1-fluoro-4-(4-nitrophenyl)sulfanyl-benzene (19.40 g, 78 mmol) in a mixture of methanol (100 mL) and tetrahydrofuran (100 mL). The resulting mixture is heated to 75° C. for 2.5 h and then cooled to room temperature. After addition of ethyl acetate (1 L), the mixture is stirred for 10 min the organic layer is decanted and collected. This procedure is repeated twice. The combined organic layers are dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude residue is first triturated twice with diethyl ether and then purified via column chromatography on silica gel (heptane/ethyl acetate 0 to 30% as eluent) to afford the desired product as a yellow solid (14.45 g, 66 mmol, 85% yield) (HPLC-MS Method 2: retention time: 1.939 min, m/z 261.0).

Workup

  1. temperaturecooled to room temperature
  2. customis decanted
  3. customcollected
  4. dry with materialThe combined organic layers are dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue is first triturated twice with diethyl ether
  8. custompurified via column chromatography on silica gel (heptane/ethyl acetate 0 to 30% as eluent)

Sources & evidence

ORD record
ord-0d313d4c469b4913ad6bd87353d98241
Source dataset
uspto-grants-2015_08
Patent number
US09096599B2

Linked notes

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