Ethanol → HCID 23511851, compound

HRID 354392Notes

Reaction equation

HRID 354392 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([F:11])=[CH:4][C:3]=1[CH2:12][C:13]([O:15]CC)=[O:14].Cl[Sn]Cl.[CH3:21][CH2:22]O>>[CH2:21]([CH:12]([C:3]1[CH:4]=[C:5]([F:11])[C:6]([NH2:8])=[CH:7][C:2]=1[F:1])[C:13]([OH:15])=[O:14])[CH3:22]

Participants

4

Reactant 3

HCID 702EthanolHCID 24479Stannous ChlorideHCID 53419355HCID 53419355, compound

Product 1

HCID 23511851HCID 23511851, compoundYield 52%

Procedure

To a stirred solution of ethyl 2,5-difluoro-4-nitrophenylacetate (5.88 g, 25.4 mol) in EtOH (100 mL), was added SnCl2 (17.2 g, 76.3 mmol) at rt. The stirring was continued for 18 hours at reflux. After removal of the solvent, the residue was dissolved in CHCl3 (100 mL) and poured into ice water-4M NaOH (40 mL of 4M NaOH in 300 mL of ice-water), extracted with CHCl3 (100 mL×2), dried over anhydrous MgSO4, and concentrated under a reduced pressure. The residue was chromatographed on silica gel (middle pressure chromatography system YAMAZEN YFLC-5404, linear gradient of hexane-EtOAc from 9:1 to 7:3, φ50 mm×500 mm, 15 mm) to give ethyl 4-amino-2,5-difluorophenylacetic acid (2.85 g, 52%) as a colorless oil. 1H-NMR (CDCl3) δ1.28 (t, J=7.3 Hz; 3H), 3.51 (s, 2H), 3.78 (brs, 2H), 4.15 (dd, J=7.2 Hz, 14.2 Hz, 2H), 6.47 (dd, J=7.5, 10.4 Hz, 1H), 6.88 (dd, J=6.7, 11.0 Hz, 1H); MS (FAB) m/z 216 (M++1).

Workup

  1. temperatureat reflux
  2. customAfter removal of the solvent
  3. dissolutionthe residue was dissolved in CHCl3 (100 mL)
  4. additionpoured into ice water-4M NaOH (40 mL of 4M NaOH in 300 mL of ice-water)
  5. extractionextracted with CHCl3 (100 mL×2)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated under a reduced pressure
  8. customThe residue was chromatographed on silica gel (middle pressure chromatography system YAMAZEN YFLC-5404, linear gradient of hexane-EtOAc from 9:1 to 7:3, φ50 mm×500 mm, 15 mm)

Sources & evidence

ORD record
ord-dba76dc2f69148d0a2685da8d2b474af
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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