Thiourea → 5-Fluoro-2-methoxyaniline

HRID 1971477Notes

Reaction equation

HRID 1971477 reaction equation
ClC(C[C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[CH:8][C:7]=1[O:13][CH3:14])C=O.[NH2:15]C(N)=S>C(O)C>[F:12][C:10]1[CH:9]=[CH:8][C:7]([O:13][CH3:14])=[C:6]([NH2:15])[CH:11]=1

Participants

4

Reactant 2

HCID 2723790ThioureaHCID 580330952-Chloro-3-(5-fluoro-2-methoxy-phenyl)-propionaldehyde

Product 1

HCID 2231055-Fluoro-2-methoxyaniline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-chloro-3-(5-fluoro-2-methoxy-phenyl)-propionaldehyde (crude from above) and thiourea (29.2 g, 0.384 mol) in ethanol (400 mL) was heated to reflux for 15 hours. The solvent was removed and the residue was diluted with dichloromethane (300 mL), sodium hydroxide (10% aqueous solution, 150 mL) and water (200 mL). The aqueous phase was extracted twice with dichloromethane (150 mL). The combined organic layer was washed with water, a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude product was recrystallized from a mixture of ethyl acetate and hexanes to give the pure product (6.5 g, 0.027 mol, 6.2% from 5-fluoro-2-methoxy-phenylamine). ESI-MS m/z calc. 238.1. found 239.2 (M+1)+ 1H NMR (CDCl3): δ 6.90-6.81 (m, 2H), 6.79-6.76 (m, 2H), 4.75 (br, 2H), 3.91 (s, 2H), 3.82 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 15 hours
  3. customThe solvent was removed
  4. additionthe residue was diluted with dichloromethane (300 mL), sodium hydroxide (10% aqueous solution, 150 mL) and water (200 mL)
  5. extractionThe aqueous phase was extracted twice with dichloromethane (150 mL)
  6. washThe combined organic layer was washed with water
  7. dry with materiala saturated aqueous solution of sodium chloride, dried over sodium sulfate
  8. customevaporated to dryness
  9. customThe crude product was recrystallized from a mixture of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-962e5827315542a1acb7df3f0de246b4
Source dataset
uspto-grants-2013_04
Patent number
US08431605B2

Reaction notes

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