Dimethylformamide → 4,4-Difluoro-4-(4'-methoxy-biphenyl-4-yl)-butyric Acid

HRID 23758Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 23758
[F:1][C:2]([F:23])([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)[C:3](N(OC)C)=O.F[C:25](F)(C1C=CC(C2C=CC(OC)=CC=2)=CC=1)[C:26]([OH:28])=[O:27].C(Cl)(=O)C(Cl)=O.CN(C)C=O.Cl.CNOC.C(N(CC)CC)C>ClCCl.C(#N)C.C(O)(C)(C)C.C1COCC1.O>[F:23][C:2]([F:1])([C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)=[CH:13][CH:14]=1)[CH2:3][CH2:25][C:26]([OH:28])=[O:27]

Komponenten

12

Edukt 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 22575053Difluoro-(4'-methoxy-biphenyl-4-yl)-acetic acidHCID 225750572,2-Difluoro-N-methoxy-2-(4'-methoxy-biphenyl-4-yl)-N-methyl-acetamide

Produkt 1

HCID 98395084,4-Difluoro-4-(4'-methoxy-biphenyl-4-yl)-butyric Acid

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 962WaterLösungsmittel2×HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 6386tert-ButanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

2,2-Difluoro-N-methoxy-2-(4′-methoxy-biphenyl-4-yl)-N-methyl-acetamide. To a solution of difluoro-(4′-methoxy-biphenyl-4-yl)-acetic acid (3.74 g, 13.4 mmol) in dichloromethane (40 mL) and acetonitrile (40 mL) is added oxalyl chloride (2.40 mL, 27.5 mmol) followed by N,N-dimethylformamide (1.05 mL, 13.6 mmol). This mixture is stirred at room temperature for 45 min and added over 10 min to a solution of N,O-dimethylhydroxylamine hydrochloride (5.23 g, 53.6 mmol) and triethylamine (11.2 mL, 80.4 mmol) in t-butanol (40 mL), THF (80 mL), and water (30 mL) at 0° C. The resulting mixture is stirred for 4 hours while warming from 0° C. to room temperature. The reaction is diluted with water and the layers separated. The organic layer is washed in succession with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified by column chromatography (silica gel, 20-30% EtOAc/hexanes) to give the desired product as a pale yellow solid.

Aufarbeitung

  1. stirringThe resulting mixture is stirred for 4 hours
  2. temperaturewhile warming from 0° C. to room temperature
  3. customthe layers separated
  4. washThe organic layer is washed in succession with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product is purified by column chromatography (silica gel, 20-30% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-7a500e444eb1402490c18621fa4f138b
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06852751B2

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