Ethyl Acetate → 2,3-Difluoro-N-(2-fluoro-4-iodophenyl)-6-[(3-methylidene azetidin-1-yl)carbonyl]aniline

HRID 1717543Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1717543
[CH3:1]C(C)([O-])C.[K+].[F:7][C:8]1[C:9]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[C:10]([C:15]([N:17]2[CH2:20][C:19](=O)[CH2:18]2)=[O:16])[CH:11]=[CH:12][C:13]=1[F:14].C(OCC)(=O)C>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[F:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([C:15]([N:17]2[CH2:20][C:19](=[CH2:1])[CH2:18]2)=[O:16])[C:9]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=1[F:30]

Komponenten

6

Edukt 3

HCID 8857Ethyl AcetateHCID 16223411{3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonylazetidin-3-oneHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 670515312,3-Difluoro-N-(2-fluoro-4-iodophenyl)-6-[(3-methylidene azetidin-1-yl)carbonyl]anilineAusbeute 21,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 74505Methyltriphenyliphosphonium bromideKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Methyl triphenylphosphonium bromide (508 mg, 1.42 mmol) was treated with potassium tert-butoxide (159 mg, 1.42 mmol) in tetrahydrofuran (5 mL) at 0° C. for 10 minutes. 1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-one (270 mg, 0.605 mmol), prepared using procedures similar to those described in Example 6, was dissolved in tetrahydrofuran (2 mL) and was added to the mixture. The mixture was stirred at ambient for 15 h and then the mixture was filtered and the filtrate was partitioned between ethyl acetate and water. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography (silica gel, 20% ethyl acetate in hexanes) gave 2,3-difluoro-N-(2-fluoro-4-iodophenyl)-6-[(3-methylideneazetidin-1-yl)carbonyl]aniline (57 mg, 0.128 mmol, 21% yield): 1H NMR (400 MHz, CDCl3): 8.56 (br s, 1H), 7.39 (dd, 1H), 7.35-7.30 (m, 1H), 7.18-7.12 (m, 1H), 6.86-6.76 (m, 1H), 6.62 (ddd, 1H), 5.14-5.00 (br, 2H), 4.74 (br d, 4H); MS (EI) for C17H2F3IN2O: 445 (MH+).

Aufarbeitung

  1. additionwas added to the mixture
  2. filtrationthe mixture was filtered
  3. customthe filtrate was partitioned between ethyl acetate and water
  4. extractionThe aqueous portion was extracted with ethyl acetate
  5. washThe combined organic portion was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-fa6bb58eb5ce4c23a6bdb84f583a5266
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07803839B2

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