Ethyl Acetate → N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide

HRID 73396Notes

Reaction equation

HRID 73396 reaction equation
[CH2:1]([C:4]1([S:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[C:12]=2[NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[F:27])(=[O:9])=[O:8])[CH2:6][CH2:5]1)C=C.C[N+]1([O-])CC[O:32]CC1.CCO[C:39]([CH3:41])=[O:40]>C1COCC1.O.[Os](=O)(=O)(=O)=O>[F:18][C:13]1[C:12]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[F:27])=[C:11]([NH:10][S:7]([C:4]2([CH2:1][CH:39]([OH:40])[CH2:41][OH:32])[CH2:6][CH2:5]2)(=[O:8])=[O:9])[CH:16]=[CH:15][C:14]=1[F:17]

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 82029Methyl morpholine oxideHCID 593863221-allyl-N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)cyclopropane-1-sulfonamide

Product 1

HCID 15985329N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamideYield 79%

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Allyl-N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)cyclopropane-1-sulfonamide (0.77 g, 1.52 mmol) and 4-methylmorpholine N-oxide (0.18 g, 1.52 mmol) were dissolved in THF (50 mL). Osmium tetroxide was added at room temperature (0.252 mmol, 0.965 mL, 4% in H2O) and the reaction mixture was stirred at room temperature for 16 hours. EtOAc was added, the organic phase was washed with water, dried (MgSO4) and concentrated under reduced pressure. The residue was purified over silica gel chromatography (eluants: EtOAc/MeOH) to obtain the titled product (0.65 g, 79%). 1H NMR (300 MHz, CDCl3+D2O): δ 7.38 (dd, J=1.8 & 10.5 Hz, 1H), 7.36 (ddd, J=2.4, 5.1 & 9.3 Hz, 1H), 7.25 (d, J=8.7 Hz, 1H), 7.02 (dd, J=9.0 & 17.7 Hz, 1H), 6.27 (dt, J=3.0, 8.7 & 17.4 Hz, 1H), 3.92 (m, 1H), 3.54 (dd, J=3.9 & 11.1 Hz, 1H), 3.39 (dd, J=6.6 & 11.1 Hz, 1H), 2.16 (dd, J=9.6 & 15.9 Hz, 1H), 1.59 (d, J=14.1 Hz, 1H), 1.41 (m, 1H), 1.26 (m, 1H), 0.83 (m, 2H); m/z=542 [M−1]−.

Workup

  1. washthe organic phase was washed with water
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified over silica gel chromatography (eluants: EtOAc/MeOH)

Sources & evidence

ORD record
ord-e3b0923a3a2d43c8aed569bcf62f47f0
Source dataset
uspto-grants-2014_09
Patent number
US08829052B2

Reaction notes

Loading…