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

HRID 605690Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 605690
[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 C17H12F3IN2O: 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-98f83dd97cdc4e33819c1d3e7b5ffa69
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07915250B2

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