Ethyl Acetate → 3-[1-Azido-2-(1,3-dioxolan-2-yl)ethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol

HRID 1672966Notes

Reaction equation

HRID 1672966 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][CH:7]1[C:9]2([CH2:12][N:11]([C:13]([C:15]3[C:20]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=4[F:29])=[C:19]([F:30])[C:18]([F:31])=[CH:17][CH:16]=3)=[O:14])[CH2:10]2)[O:8]1.[N-:32]=[N+:33]=[N-:34].[Na+].C(OCC)(=O)C>CN(C)C=O>[N:32]([CH:7]([C:9]1([OH:8])[CH2:10][N:11]([C:13]([C:15]2[CH:16]=[CH:17][C:18]([F:31])=[C:19]([F:30])[C:20]=2[NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[O:14])[CH2:12]1)[CH2:6][CH:2]1[O:3][CH2:4][CH2:5][O:1]1)=[N+:33]=[N-:34]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 33557Sodium AzideHCID 866212736-{[2-(1,3-dioxolan-2-ylmethyl)-1-oxa-5-azaspiro[2.3]hex-5-yl]carbonyl}-2,3-difluoro-N-(2-fluoro-4-iodophenyl)aniline

Product 1

HCID 866212743-[1-Azido-2-(1,3-dioxolan-2-yl)ethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-olYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-{[2-(1,3-Dioxolan-2-ylmethyl)-1-oxa-5-azaspiro[2.3]hex-5-yl]carbonyl}-2,3-difluoro-N-(2-fluoro-4-iodophenyl)aniline (31 mg, 0.057 mmol) was dissolved in dimethylformamide (0.5 mL) and sodium azide (20 mg, 0.308 mmol) was added. The mixture was stirred at ambient for 22 h. The mixture was partitioned between ethyl acetate and 5% lithium chloride. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with water, brine, then was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography (silica gel, 50% ethyl acetate in hexanes) gave 3-[1-azido-2-(1,3-dioxolan-2-yl)ethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol (25 mg, 0.042 mmol, 74% yield): MS (EI) for C21H19F3IN5O4: 590 (MH+).

Workup

  1. customThe mixture was partitioned between ethyl acetate and 5% lithium chloride
  2. extractionThe aqueous portion was extracted with ethyl acetate
  3. washThe combined organic portion was washed with water, brine
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c21702658f9c478b84a95a00d3f283b9
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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