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

HRID 2218466노트

반응식

HRID 2218466 반응식
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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-694c499fbd3c42d79ad76cfdd9625917
출처 데이터셋
uspto-grants-2008_08
특허 번호
US07411001B2

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