Acetic Acid → 4-(6-Chloropyrimidin-4-yl)-3-methoxyaniline

HRID 475873Notes

Reaction equation

HRID 475873 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][C:9]=2[O:17][CH3:18])[N:5]=[CH:4][N:3]=1.C(O)(=O)C>CCO.[Fe]>[Cl:1][C:2]1[N:3]=[CH:4][N:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][C:9]=2[O:17][CH3:18])[CH:7]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 580756184-Chloro-6-(2-methoxy-4-nitrophenyl)pyrimidine

Product 1

HCID 580753154-(6-Chloropyrimidin-4-yl)-3-methoxyanilineYield 93.9%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 4-chloro-6-(2-methoxy-4-nitrophenyl)pyrimidine (0.6 g, 2.259 mmol) in EtOH (Ratio: 2.000, Volume: 10 mL) was stirred at 80° C. to make most of the material solublized, Acetic Acid 20% (Ratio: 1.000, Volume: 5 mL) and iron powder (0.883 g, 15.81 mmol) were added. The resulting mixture was refluxed for 1 h. The reaction was concentrated under vacuum. The residue was partitioned between EtOAc/1.0 M aqueous NaOH. The aqueous layer was extracted with EtOAc (3×20 ml). The combined organic layers were washed with aqueous sodium bicarbonate (2×20 ml) and brine (20 ml), dried over magnesium sulfate, filtered and concentrated. The residue was purified via Biotage Horizon system (25 g column of Thomson Single Step, EtOAc/Hexane, Griadient: 0%˜80%). Desired fractions were collected, concentrated and the residue was triturated with DCM to get 0.5 g (82%) of product as light-yellow solid. LC-MS (M+H)+=236. 1H NMR (400 MHz, CDCl3) δ ppm 3.91 (s, 3H) 4.07 (br. s., 2H, NH2) 6.27 (d, J=2.26 Hz, 1H) 6.40 (dd, J=8.53, 2.26 Hz, 1H) 8.04 (d, J=1.25 Hz, 1H) 8.07 (d, J=8.28 Hz, 1H) 8.91 (d, J=1.25 Hz, 1H).

Workup

  1. temperatureThe resulting mixture was refluxed for 1 h
  2. concentrationThe reaction was concentrated under vacuum
  3. customThe residue was partitioned between EtOAc/1.0 M aqueous NaOH
  4. extractionThe aqueous layer was extracted with EtOAc (3×20 ml)
  5. washThe combined organic layers were washed with aqueous sodium bicarbonate (2×20 ml) and brine (20 ml)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified via Biotage Horizon system (25 g column of Thomson Single Step, EtOAc/Hexane, Griadient: 0%˜80%)
  10. customDesired fractions were collected
  11. concentrationconcentrated
  12. customthe residue was triturated with DCM

Sources & evidence

ORD record
ord-06d8d38e877d4521b2302363fc2fcde3
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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