p-Toluenesulfonic acid monohydrate → N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide

HRID 1829094Notes

Reaction equation

HRID 1829094 reaction equation
CC1(C)[O:6][C@@H: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.CO.O.CC1C=CC(S(O)(=O)=O)=CC=1.O>CCOC(C)=O>[OH:6][C@H: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

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 22242641Methanol--water (1/1)HCID 86591458N-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide

Product 1

HCID 9826528N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

N-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (0.210 g, 0.40 mmol) was suspended in 10:1 methanol/H2O and pTsOH.H2O (0.008 g, 0.04 mmol) was added. The mixture was stirred at ambient temperature for 18 hrs, during which all solids dissolved to give a colorless, clear solution. The solution was diluted with EtOAc. The organic solution was washed with sodium bicarbonate (2×), brine (1×) and dried over Na2SO4. After filtration, the filtrate was concentrated, and recrystallized from EtOAc and heptane. This solid was washed with heptane-CH2Cl2 (1:1 and dried in vacuo at 60 C to give N-((R)-2,3-Dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide as a white solid, (0.136 g, 70%). Product shrinks at 90.8 C, melts at 115–117° C. Analysis shows C, 40.92; H, 3.16; N, 5.41, F, 11.30; I, 23.92 (6.75% EtOAc, 0.96% heptane).

Workup

  1. additionwas added
  2. dissolutiondissolved
  3. customto give a colorless, clear solution
  4. washThe organic solution was washed with sodium bicarbonate (2×), brine (1×)
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated
  8. customrecrystallized from EtOAc and heptane
  9. washThis solid was washed with heptane-CH2Cl2 (1:1
  10. customdried in vacuo at 60 C

Sources & evidence

ORD record
ord-d0041437ecb3473a90c6baf95aaa0e8c
Source dataset
uspto-grants-2006_06
Patent number
US07060856B2

Reaction notes

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