(4-Amino-3-chloro-phenyl)-acetic acid ethyl ester → Ethyl (3-chloro-4-{[(2-chloro-5-{[(3-chlorophenyl)methyl]oxy}phenyl)carbonyl]amino}phenyl)acetate

HRID 1879106

反応式

HRID 1879106 の反応式
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.Cl.CN(C)CCN=C=NCC.[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:34][C:33]=1[Cl:44]>ClCCl.O>[Cl:44][C:33]1[CH:34]=[C:35]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH:36]=[CH:37][C:32]=1[NH:31][C:4]([C:3]1[CH:7]=[C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[CH:9]=[CH:10][C:2]=1[Cl:1])=[O:6]

参加物

6

反応物 3

HCID 17859298(4-Amino-3-chloro-phenyl)-acetic acid ethyl esterHCID 57494384N-[2-(dimethylamino)ethyl]-N'-ethylcarbodiimide hydrochloride2 回HCID 597600492-Chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid

生成物 1

HCID 59163369Ethyl (3-chloro-4-{[(2-chloro-5-{[(3-chlorophenyl)methyl]oxy}phenyl)carbonyl]amino}phenyl)acetate

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

A solution of 2-chloro-5-{[(3-chlorophenyl)methyl]oxy}benzoic acid (230 mg, 0.77 mmol) in dichloromethane (3 ml) was treated with N-[2-(dimethylamino)ethyl]-N′-ethylcarbodiimide hydrochloride (178 mg, 0.93 mmol, 1.2 eq) and stirred at room temperature for 30 minutes. A solution of ethyl (4-amino-3-chlorophenyl)acetate (198 mg, 0.93 mmol, 1.2 eq) in dichloromethane (2 ml) was added and the resulting mixture heated at 40° C. overnight. As some starting material was still present, another 100 mg of N-[2-(dimethylamino)ethyl]-N′-ethylcarbodiimide hydrochloride were added and the mixture heated at 40° C. for another 2 hours. On cooling, the mixture was diluted with dichloromethane (50 ml) and water (30 ml), the layers separated and the aqueous layer extracted again into dichloromethane (50 ml). Organic layers combined, washed with brine, dried over magnesium sulphate and evaporated to afford the title compound as a yellow oil. The aqueous layer containing an insoluble solid was evaporated in vacuo, the residue purified by SCX cartridge eluting with methanol to afford a further crop of the title compound as a yellow oil (72 mg total). MS (ES+) m/z 492 [M+H]+ (C24H2035Cl3NO4). 1H-NMR (400 MHz, d6-DMSO) δ 1.20 (3H, t, J 7.2), 3.72 (2H, s), 4.10 (2H, q, J 7.2), 5.20 (2H, s), 7.15-7.62 (10H, m).

後処理

  1. temperaturethe resulting mixture heated at 40° C. overnight
  2. temperaturethe mixture heated at 40° C. for another 2 hours
  3. temperatureOn cooling
  4. customthe layers separated
  5. extractionthe aqueous layer extracted again into dichloromethane (50 ml)
  6. washwashed with brine
  7. dry with materialdried over magnesium sulphate
  8. customevaporated

出典と根拠

ORDレコード
ord-6aa6f715cbeb4aa39954dc9070533e45
出典データセット
uspto-grants-2012_11
特許番号
US08314147B2

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