3-Aminobenzamide → 3-[2-(4-Bromo-2-chloro-phenoxy)acetyl-amino]-benzamide

HRID 1945388

反応式

HRID 1945388 の反応式
[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([OH:10])=O)=[C:4]([Cl:13])[CH:3]=1.[NH2:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18]([NH2:20])=[O:19].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Br:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([NH:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=2)[C:18]([NH2:20])=[O:19])=[O:10])=[C:4]([Cl:13])[CH:3]=1

参加物

7

反応物 5

HCID 16453-AminobenzamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6931572-(4-Bromo-2-chlorophenoxy)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

生成物 1

HCID 248111063-[2-(4-Bromo-2-chloro-phenoxy)acetyl-amino]-benzamide収率 94.6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 4-bromo-2-chloro-phenol (2.0 g, 9.64 mmol) and anhydrous potassium carbonate (4.0 g, 28.92 mmol) in dry DMF (30 ml) was heated at 60° C. for 1 h under Ar atmosphere. The mixture was then cooled to room temperature and ethyl chloroacetate (1.24 ml, 11.57 mmol) was added through septum using syringe. The mixture was stirred overnight at room temperature and poured into water with stirring. Stirring continued for 10 min, and then partitioned between ethyl acetate and water. The organic phase washed with brine, dried (anhydrous MgSO4), and concentrated. The residue was purified by silica gel column chromatography (n-Hexane:Ethyl acetate:MeOH=15:3:1) to give (4-Bromo-2-chloro-phenoxy)-acetic acid ethyl ester as a colorless oil (2.98 (2.83) g, >100% yield). To (4-bromo-2-chloro-phenoxy)-acetic acid (132.8 mg, 0.5 mmol), 3-amino-benzamide (102.2 mg, 0.75 mmol), N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide HCl (EDC) (143.8 mg, 0.75 mmol) and 1-hydroxybenzotriazole (HOBt) (101.4 mg, 0.75 mmol) in DMF (5 ml) was added N,N-diisopropylethylamine, redistilled (DIPEA) (0.13 ml, 0.75 mmol). The mixture was stirred overnight, and then partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography (CH2CH2:MeOH=10:1) to give 3-[2-(4-bromo-2-chloro-phenoxy)acetyl-amino]-benzamide as a white solid (181.4 mg, 94.6% yield).

後処理

  1. distillationredistilled (DIPEA) (0.13 ml, 0.75 mmol)
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with brine
  4. dry with materialdried (MgSO4 anh)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash column chromatography (CH2CH2:MeOH=10:1)

出典と根拠

ORDレコード
ord-25887fe2ee544fb98746a2423fa32c33
出典データセット
uspto-grants-2013_03
特許番号
US08394799B2

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