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

HRID 605691노트

반응식

HRID 605691 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 30318Osmium Tetroxide촉매

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-125e3f72526f46f1ac6bec80d66bb562
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915250B2

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