4-Fluoroaniline → HCID 12140011, compound

HRID 2170445Notes

Reaction equation

HRID 2170445 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.I[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1.C([O-])([O-])=O.[K+].[K+].N1CCC[C@H]1C(O)=O>[Cu]I.CCOC(C)=O.O.CS(C)=O>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 97314-FluoroanilineHCID 11430Potassium CarbonateHCID 696764-IodoanisoleHCID 145742L-Proline

Product 1

HCID 12140011HCID 12140011, compoundYield 77.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-fluoroaniline (78.63 g, 0.708 mol), 4-iodoanisole (138.00 g, 0.590 mol), anhydrous K2CO3 (122.23 g, 0.884 mol), CuI (11.23 g, 58.96 mmol) and L-proline (13.58 g, 0.118 mol) was mixed together in a dry 1 L three-necked round-bottomed flask fitted with a stirring bar, a reflux condenser and an argon inlet. Anhydrous DMSO (300 mL) was added at room temperature. The reaction mixture was stirred and heated to 90° C. for 20 hours under argon. Then, the mixture was cooled to room temperature and hydrolyzed with water (300 mL). EtOAc (200 mL) was added to partition the solution. The EtOAc layer was separated. The aqueous layer was extracted with 100 mL of EtOAc. The EtOAc layers were combined, washed with brine (2×100 mL) and dried over anhydrous MgSO4 (50 g). The solvent was removed under reduced pressure. The brown oil residue was purified by flash column chromatography (silica gel, Hexanes/EtOAc=9/1 v/v) to afford 4-fluoro-N-(4-methoxyphenyl)aniline (1c) as a yellow solid product, 99.70 g, 77.8% yield. M.p. 46-48° C. MS (ESI) m/z 218.1 [M+H]+, 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (bs, 1H), 7.03-6.98 (m, 4H), 6.93-6.82 (m, 4H), 3.70 (s, 3H).

Workup

  1. additionwas mixed together in a dry 1 L three-necked round-bottomed flask
  2. customfitted with a stirring bar, a reflux condenser and an argon inlet
  3. customto partition the solution
  4. customThe EtOAc layer was separated
  5. extractionThe aqueous layer was extracted with 100 mL of EtOAc
  6. washwashed with brine (2×100 mL)
  7. dry with materialdried over anhydrous MgSO4 (50 g)
  8. customThe solvent was removed under reduced pressure
  9. customThe brown oil residue was purified by flash column chromatography (silica gel, Hexanes/EtOAc=9/1 v/v)

Sources & evidence

ORD record
ord-504b5a01e3294c48beb0ffd590006cd8
Source dataset
uspto-grants-2015_06
Patent number
US09051267B2

Reaction notes

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