Methyl morpholine oxide → 1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(hydroxymethyl)azetidin-3-ol

HRID 1808948Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1808948
[F:1][C:2]1[C:16]([F:17])=[CH:15][CH:14]=[C:13]([C:18]([N:20]2CC(=C)C2)=[O:19])[C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:6]=1[F:12].C[N+]1([O-])CC[O:29][CH2:28]C1.[CH3:33][C:34]([CH3:36])=[O:35].O>[Os](=O)(=O)(=O)=O>[F:1][C:2]1[C:3]([NH:4][C:5]2[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:6]=2[F:12])=[C:13]([C:18]([N:20]2[CH2:36][C:34]([CH2:28][OH:29])([OH:35])[CH2:33]2)=[O:19])[CH:14]=[CH:15][C:16]=1[F:17]

Komponenten

5

Edukt 3

HCID 82029Methyl morpholine oxideHCID 18366337Propan-2-one--water (1/1)HCID 670515312,3-Difluoro-N-(2-fluoro-4-iodophenyl)-6-[(3-methylidene azetidin-1-yl)carbonyl]aniline

Produkt 1

HCID 162234131-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(hydroxymethyl)azetidin-3-olAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 30318Osmium TetroxideKatalysator

Versuchsvorschrift

2,3-Difluoro-N-(2-fluoro-4-iodophenyl)-6-[(3-methylideneazetidin-1-yl)carbonyl]aniline (56 mg, 0.126 mmol) and 4-methylmorpholine N-oxide (44 mg, 0.376 mmol) were dissolved in acetone/water (4:1; 10 mL) and osmium tetroxide (4 wt. % in water; 0.7 mL) was added. The solution was stirred at ambient for 4 h, then was quenched with saturated sodium bisulfite (2 mL) and concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography (silica gel, 80% ethyl acetate in hexanes) and then reverse phase HPLC gave 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(hydroxymethyl)azetidin-3-ol (17 mg, 0.036 mmol, 28% yield): 1H NMR (400 MHz, CDCl3): 8.43 (br s, 1H), 7.40 (dd, 1H), 7.35-7.31 (m, 1H), 7.16-7.10 (m, 1H), 6.81 (ddd, 1H), 6.61 (ddd, 1H), 4.25-4.00 (m, 4H), 3.78 (s, 2H); MS (EI) for C17H14F3IN2O3: 479 (MH+).

Aufarbeitung

  1. customwas quenched with saturated sodium bisulfite (2 mL)
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between ethyl acetate and water
  4. washThe organic portion was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-a132cca6e8e447599a01f3314b0b2235
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362002B2

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