Ethyl Acetate → 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

HRID 1809027Notes

Reaction equation

HRID 1809027 reaction equation
CC(C1C=C(C(C)C)C=C(C(C)C)C=1S([O:19][CH:20]([C:27]1(O)[CH2:30][N:29]([C:31]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[C:35]([F:40])[C:34]=2[NH:41][C:42]2[CH:47]=[CH:46][C:45]([I:48])=[CH:44][C:43]=2[F:49])=[O:32])[CH2:28]1)[CH2:21][CH:22]1[O:26][CH2:25][CH2:24][O:23]1)(=O)=O)C.[H-].[Na+].C(OCC)(=O)C>O1CCCC1>[O:26]1[CH2:25][CH2:24][O:23][CH:22]1[CH2:21][CH:20]1[C:27]2([CH2:30][N:29]([C:31]([C:33]3[C:34]([NH:41][C:42]4[CH:47]=[CH:46][C:45]([I:48])=[CH:44][C:43]=4[F:49])=[C:35]([F:40])[C:36]([F:39])=[CH:37][CH:38]=3)=[O:32])[CH2:28]2)[O:19]1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 866212721-[1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]-2-(1,3-dioxolan-2-yl)ethyl 2,4,6-tris(1-methylethyl)benzenesulfonate

Product 1

HCID 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)anilineYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

1-[1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]-2-(1,3-dioxolan-2-yl)ethyl 2,4,6-tris(1-methylethyl)benzenesulfonate (50 mg, 0.060 mmol) was dissolved in tetrahydrofuran (1 mL) and was cooled to 0° C. Sodium hydride (60 wt % dispersion in oil; 7 mg, 0.18 mmol) was added and the mixture was stirred at 0° C. for 45 minutes. The mixture was quenched with saturated sodium bicarbonate solution and partitioned with ethyl acetate. 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, 50% ethyl acetate in hexanes) gave 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, 94% yield): MS (EI) for C21H18F3IN2O4: 547 (MH+).

Workup

  1. customThe mixture was quenched with saturated sodium bicarbonate solution
  2. custompartitioned with ethyl acetate
  3. extractionThe aqueous portion was extracted with ethyl acetate
  4. washThe combined organic portion was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-937f6a66816440f0b79103be2a7d2d52
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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