18-Crown-6 → (2-Fluoro-6-nitrophenylamino)acetic acid ethyl ester

HRID 558940Notes

Reaction equation

HRID 558940 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1F.Cl.[CH2:13]([O:15][C:16](=[O:19])[CH2:17][NH2:18])[CH3:14].[F-].[K+].C1OCCOCCOCCOCCOCCOC1.C(N(C(C)C)CC)(C)C>C(#N)C>[CH2:13]([O:15][C:16](=[O:19])[CH2:17][NH:18][C:3]1[C:4]([N+:8]([O-:10])=[O:9])=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])[CH3:14]

Participants

7

Reactant 5

HCID 2855718-Crown-6HCID 813351,2-Difluoro-3-nitrobenzeneHCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 2723640Glycine ethyl ester, hydrochloride

Product 1

HCID 67000141(2-Fluoro-6-nitrophenylamino)acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1,2-difluoro-3-nitrobenzene from Example B1 (1.9 g, 12 mmol) in acetonitrile (75 ml) were added glycine ethyl ester hydrochloride (1.7 g, 12 mmol), potassium fluoride (1.2 g, 20 mmol), 18-crown-6 (309 mg, 1.2 mmol) and diisopropylethylamine (4.6 ml, 26 mmol). The mixture was stirred at reflux for 3 h, cooled and evaporated in vacuo. The residue was partitioned between water and EtOAc. The organic layer was washed with brine, filtered and evaporated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 20:80); yield 2.1 g, 73%.

Workup

  1. temperatureat reflux for 3 h
  2. temperaturecooled
  3. customevaporated in vacuo
  4. customThe residue was partitioned between water and EtOAc
  5. washThe organic layer was washed with brine
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 20:80)

Sources & evidence

ORD record
ord-9f4ca0a11f0c4f95b0e06008b165e582
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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