Methyl 3-amino-4-methylbenzoate → 4-Methyl-3-[3-(2,3,4-trimethoxy-phenyl)-acryloylamino]-benzoic acid methyl ester

HRID 383590

反応式

HRID 383590 の反応式
[CH3:1][O:2][C:3]1[C:13]([O:14][CH3:15])=[C:12]([O:16][CH3:17])[CH:11]=[CH:10][C:4]=1/[CH:5]=[CH:6]/[C:7](Cl)=[O:8].[NH2:18][C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][C:28]=1[CH3:29])[C:22]([O:24][CH3:25])=[O:23]>C(Cl)Cl.N1C=CC=CC=1>[CH3:25][O:24][C:22](=[O:23])[C:21]1[CH:26]=[CH:27][C:28]([CH3:29])=[C:19]([NH:18][C:7](=[O:8])[CH:6]=[CH:5][C:4]2[CH:10]=[CH:11][C:12]([O:16][CH3:17])=[C:13]([O:14][CH3:15])[C:3]=2[O:2][CH3:1])[CH:20]=1

参加物

5

反応物 2

HCID 337778Methyl 3-amino-4-methylbenzoateHCID 13270107trans-2,3,4-Trimethoxycinnamic acid chloride

生成物 1

HCID 52034944-Methyl-3-[3-(2,3,4-trimethoxy-phenyl)-acryloylamino]-benzoic acid methyl ester収率 61.2%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve trans-2,3,4-Trimethoxycinnamic acid (50) (200 mg, 0.84 mmol) in anhydrous DCM (4.4 mL) at it and add anhydrous DMF (3 drops, cat. amount). Then add slowly oxalyl chloride (96 μL, 1.09 mmol) stir the turbid mixture for additional 2 h at rt. Remove solvent and dry the residue in oil pump vacuum to obtain trans-2,3,4-Trimethoxycinnamic acid chloride (51) (ca. 0.84 mmol) as an yellow solid. Dissolve acid chloride (51) (108 mg, 0.42 mmol) in anhydrous DCM (4.0 mL) and add it to an ice cooled solution of Methyl 3-amino-4-methylbenzoate (52) (69 mg, 0.42 mmol) in anhydrous DCM (2.0 mL) and anhydrous pyridine (1.2 mL). Stir the resulting reaction mixture at rt overnight. Pour the reaction mixture into ice cooled 1M aqu. HCl, extract with EtOAc (3×), wash the combined organic layer with brine and dry it with Na2SO4. Purify the crude product by filtration through a short pad of silica gel with EtOAc and remove solvent to obtain 4-Methyl-3-[3-(2,3,4-trimethoxy-phenyl)-acryloylamino]-benzoic acid methyl ester (53) (99 mg, 61%) as a light yellow solid. 1H NMR (400 MHz, CDCl3): 2.35 (s, 3H); 3.87 (s, 3H); 3.88 (s, 6H); 3.91 (br.s, 3H); 6.59 (d, 1H, J=15.6 Hz); 6.68 (d, 1H, J=8.6 Hz); 7.08 (br.s, 1H); 7.20-7.29 (m, 2H); 7.77 (br.d, 1H, J=8.6 Hz); 7.90 (d, 1H, J=15.6 Hz); 8.55 (br.s 1H).

後処理

  1. customthe resulting reaction mixture at rt overnight
  2. additionPour the reaction mixture into ice
  3. temperaturecooled 1M aqu
  4. extractionHCl, extract with EtOAc (3×)
  5. washwash the combined organic layer with brine
  6. dry with materialdry it with Na2SO4
  7. customPurify the crude product
  8. filtrationby filtration through a short pad of silica gel with EtOAc
  9. customremove solvent

出典と根拠

ORDレコード
ord-7982ae49c0a34d529ea06a6758932319
出典データセット
uspto-grants-2013_02
特許番号
US08367677B2

関連ノート

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