Diisopropylethylamine → 5-chloro-2-(2-chloro-4-iodo-phenylamino)-N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-benzamide

HRID 2218466Notes

Reaction equation

HRID 2218466 reaction equation
FC1C(O[C:9](=[O:28])[C:10]2[CH:15]=[C:14]([Cl:16])[C:13]([F:17])=[C:12]([F:18])[C:11]=2[NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[Cl:27])=C(F)C(F)=C(F)C=1F.[CH3:33][C:34]1([CH3:42])[O:38][CH:37]([CH2:39][O:40][NH2:41])[CH2:36][O:35]1.C(N(C(C)C)CC)(C)C>O1CCCC1>[Cl:16][C:14]1[C:13]([F:17])=[C:12]([F:18])[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=2[Cl:27])=[C:10]([CH:15]=1)[C:9]([NH:41][O:40][CH2:39][CH:37]1[CH2:36][O:35][C:34]([CH3:42])([CH3:33])[O:38]1)=[O:28]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10240948O-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]hydroxylamineHCID 233984935-Chloro-2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-benzoic acid pentafluorophenyl ester

Product 1

HCID 222864765-chloro-2-(2-chloro-4-iodo-phenylamino)-N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-benzamideYield 67.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 5-chloro-2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-benzoic acid pentafluorophenyl ester (5.80 g, 9.51 mmol) is freshly distilled tetrahydrofuran (40 mL) was added O-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (1.54 g, 10.5 mmol) and diisopropylethylamine (1.8 mL, 10.5 mmol). After 20 hours, the mixture was partitioned between ethyl acetate and water. The organic layer was washed twice with water and twice with saturated brine solution. The organic layer was collected, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by crystallization in ethyl acetate/hexanes affording 5-chloro-2-(2-chloro-4-iodo-phenylamino)-N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-benzamide as a white solid (3.7 g, 67.9%): 1H NMR (400 MHz; CDCl3) δ 9.82 (bs, 1H), 8.10 (bs, 1H), 7.68 (s, 1H), 7.47 (bs, 1H), 7.40-7.43 (m, 1H), 6.44-6.47 (m, 1H), 4.40 (bs, 1H), 3.97-4.20 (m, 3H), 3.77 (t, 1H, J=8.0), 1.44 (s, 3H), 1.37 (s, 3H); MS (APCI+)=573.0/575.0.

Workup

  1. customthe mixture was partitioned between ethyl acetate and water
  2. washThe organic layer was washed twice with water and twice with saturated brine solution
  3. customThe organic layer was collected
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by crystallization in ethyl acetate/hexanes

Sources & evidence

ORD record
ord-694c499fbd3c42d79ad76cfdd9625917
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

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