p-Toluenesulfonic acid → N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide

HRID 1062293Notes

Reaction equation

HRID 1062293 reaction equation
CC1(C)[O:6][CH:5]([CH2:7][O:8][NH:9][C:10](=[O:28])[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])[CH2:4][O:3]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.O.C(O)C>[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10](=[O:28])[C:11]1[CH:16]=[CH:15][C:14]([F:17])=[C:13]([F:18])[C:12]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=1[F:27]

Participants

6

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 22061666N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide

Product 1

HCID 10206158N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamideYield 46.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirring solution of N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (0.907 g, 1.74 mmol) in methanol (10 mL) and water (1 mL) at ambient temperature was added p-toluene sulfonic acid (0.032 g, 0.17 mmol). After stirring for 18 hours the reaction mixture was concentrated in vacuo and the affording residue was partitioned between ethyl acetate and water. The organic layers were washed twice with water and once with saturated brine solution. Organic layers were collected, dried over Na2SO4, filtered and concentrated in vacuo affording a light brown solid, which was dissolved in ethanol and precipitated with water to afford N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide as a white solid (0.387 g). m.p.=83-85° C.; 1NMR (400 MHz, DMSO-d6) 11.87 (s, 1H), 8.69 (s, 1H), 7.56 (d, 1H, J=11.0), 7.33-7.39 (m, 2H), 7.19 (dd, 1H, J=16.6, 9.0), 6.62-6.68 (cm, 1H), 4.82 (d, 1H, J=4.2), 4.58 (t, 1H, J=5.5), 3.84-3.87 (m, 1H), 3.66-3.72 (m, 2H), 3.3 (2H, partially hidden by HDO); MS(APCI+)=483.0; Anal.calcd/found for C16H14F3IN2O4.0.3 H2O: C, 39.41/39.02; H, 3.02/2.93; N, 5.75, 5.81; F, 11.69/11.68.

Workup

  1. concentrationwas concentrated in vacuo
  2. customthe affording residue was partitioned between ethyl acetate and water
  3. washThe organic layers were washed twice with water and once with saturated brine solution
  4. customOrganic layers were collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customaffording a light brown solid, which
  9. customprecipitated with water

Sources & evidence

ORD record
ord-fc6a851df1fd48f9b2cc769e1ff42c09
Source dataset
uspto-grants-2005_11
Patent number
US06960614B2

Reaction notes

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