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

HRID 1062292Notes

Reaction equation

HRID 1062292 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>[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

5

Reactant 2

HCID 6101p-Toluenesulfonic acid2×HCID 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)benzamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

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 (3.03 g, 5.81 mmol) in methanol (30 mL) and water (3 mL) at ambient temperature was added p-toluene sulfonic acid (0.11 g, 0.581 mmol). After 18 hours another 0.11 g of added p-toluene sulfonic acid and 2 mL of water was added. After an additional 24 hours the reaction mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The organic layer was washed twice with saturated NaHCO3 solution and twice with saturated brine solution. The organic layers were collected, dried over Na2SO4, filtered and concentrated in vacuo affording a light brown solid, which was crystallized from ethyl acetate/hexanes to afford N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide as a white solid. m.p.=135.5-137.3° C.; 1NMR (400 MHz, DMSO-d6) δ 11.87 (s, 1H), 8.69 (s, 1H), 7.54 (dd, 1H, J=10.9, 1.5), 7.32-7.38 (m, 2H), 7.17 (dd, 1H, J=16.8, 9.0), 6.61-6.66 (cm, 1H), 4.82 (bs, 1H), 4.58 (bs, 1H), 3.84-3.85 (m, 1H), 3.71-3.64 (cm, 2H), 3.33 (2H, partially hidden by HDO); MS(APCI+)=483.0; Anal.calcd/found for C16H14F3IN2O4: C, 39.85/40.12; H, 2.93/2.84; N, 5.81/5.65; F, 11.82/11.47.

Workup

  1. concentrationAfter an additional 24 hours the reaction mixture was concentrated in vacuo
  2. customThe residue was partitioned between ethyl acetate and water
  3. washThe organic layer was washed twice with saturated NaHCO3 solution and twice with saturated brine solution
  4. customThe organic layers were collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customaffording a light brown solid, which
  9. customwas crystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ddfaa1ba554048078b91a712285e9542
Source dataset
uspto-grants-2005_11
Patent number
US06960614B2

Reaction notes

Loading…