Ethyl Acetate → Tert-butyl 4-amino-3-chloro-2-fluorobenzoate

HRID 2406313Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2406313
[Cl:1]N1C(=O)CCC1=O.[NH2:9][C:10]1[CH:22]=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[C:12]([F:23])[CH:11]=1.C(OCC)(=O)C>CN(C)C=O.[Cl-].[Na+].O>[NH2:9][C:10]1[C:22]([Cl:1])=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])=[C:12]([F:23])[CH:11]=1.[NH2:9][C:10]1[CH:22]=[CH:21][C:13]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])=[C:12]([F:23])[C:11]=1[Cl:1]

Komponenten

7

Edukt 3

HCID 8857Ethyl AcetateHCID 31398ChlorosuccinimideHCID 10058989Tert-butyl 4-amino-2-fluorobenzoate

Produkt 2

HCID 68684306Tert-butyl 4-amino-5-chloro-2-fluorobenzoateAusbeute 23 %HCID 86687946Tert-butyl 4-amino-3-chloro-2-fluorobenzoateAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

To a solution of N-chlorosuccinimide (950 mg, 7.1 mmol) in N,N-dimethylformamide (25 mL) was added dropwise a solution of tert-butyl 4-amino-2-fluorobenzoate (1.5 g, 7.1 mmol) in N,N-dimethylformamide (22 mL). The resulting mixture was stirred at room temperature for 3 hours and then brine solution (80 mL) and ethyl acetate (100 mL) were added. The organic phase was collected and washed three times with brine (50 mL). Combined organic phases were dried on magnesium sulphate and evaporated under reduced pressure. Purification of the residue via silica gel column chromatography (4% EtOAc in iso-hexane) gave tert-butyl 4-amino-5-chloro-2-fluorobenzoate (400 mg, 23%, 1H NMR (400 MHz, DMSO-d6): δ 7.63 (d, J=7.6 Hz, 1H), 6.55 (d, J=13.2 Hz, 1H), 6.46 (brs, 2H), 1.52 (s, 9H)) and tert-butyl 4-amino-3-chloro-2-fluorobenzoate (490 mg, 28%, 1H NMR (400 MHz, DMSO-d6): δ 7.52 (t, J=8.4 Hz, 1H), 6.64 (dd, J=1.2 Hz and J=8.4 Hz, 1H), 6.50 (brs, 2H), 1.53 (s, 9H)) both as a white solid.

Aufarbeitung

  1. customThe organic phase was collected
  2. washwashed three times with brine (50 mL)
  3. customCombined organic phases were dried on magnesium sulphate
  4. customevaporated under reduced pressure
  5. customPurification of the residue via silica gel column chromatography (4% EtOAc in iso-hexane)

Quellen und Nachweise

ORD-Eintrag
ord-a75468e349ef425598185566ee38c42d
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08809331B2

Notizen zur Reaktion

Wird geladen…