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

HRID 605691ノート

反応式

HRID 605691 の反応式
[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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 30318Osmium Tetroxide触媒

実験手順

2,3-Difluoro-N-(2-fluoro-4-iodophenyl)-6-[(3-methylidene azetidin-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 bisulfate (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+).

後処理

  1. customwas quenched with saturated sodium bisulfate (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

出典と根拠

ORDレコード
ord-125e3f72526f46f1ac6bec80d66bb562
出典データセット
uspto-grants-2011_03
特許番号
US07915250B2

反応ノート

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