18-Crown-6 → 3-(2-Fluoro-6-nitrophenylamino)propionic acid methyl ester

HRID 558948Notes

Reaction equation

HRID 558948 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.[CH3:13][O:14][C:15](=[O:19])[CH2:16][CH2:17][NH2:18].[F-].[K+].C1OCCOCCOCCOCCOCCOC1.C(N(C(C)C)CC)(C)C>C(#N)C>[CH3:13][O:14][C:15](=[O:19])[CH2:16][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]

Participants

7

Reactant 5

HCID 2855718-Crown-6HCID 813351,2-Difluoro-3-nitrobenzeneHCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 2734767Methyl 3-aminopropanoate hydrochloride

Product 1

HCID 574707783-(2-Fluoro-6-nitrophenylamino)propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1,2-difluoro-3-nitrobenzene from Example B1 (500 mg, 3.1 mmol) in acetonitrile (25 ml) were added β-alanine methyl ester hydrochloride (440 mg, 3.1 mmol), potassium fluoride (310 mg, 5.3 mmol), 18-crown-6 (84 mg, 0.3 mmol) and diisopropylethylamine (1.2 ml, 7 mmol). The mixture was stirred at reflux for 2 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 25:75); yield 650 mg, 86%.

Workup

  1. temperatureat reflux for 2 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 25:75)

Sources & evidence

ORD record
ord-699e18f54e484f1ab2b4ce038e55be24
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

Loading…