Ethanol → [5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester

HRID 1256684

反応式

HRID 1256684 の反応式
N#N.C(O)C.Cl.[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1B(O)O.[CH3:17][O:18][C:19](=[O:27])[CH2:20][C:21]1[S:22][C:23](Br)=[CH:24][CH:25]=1>O.C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:17][O:18][C:19](=[O:27])[CH2:20][C:21]1[S:22][C:23]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[NH2:7])=[CH:24][CH:25]=1

参加物

8

反応物 4

HCID 702EthanolHCID 947NitrogenHCID 12403315Methyl 2-(5-bromothiophen-2-yl)acetateHCID 164270902-Aminophenylboronic acid hydrochloride

生成物 1

HCID 16116160[5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester収率 51.3%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒2 回

反応条件

温度
100 °C

実験手順

(The following reaction is carried out in an N2 atmosphere.) Ethanol (3.7 mL), tetrakis-(triphenylphosphine)-palladium(0) (289 mg, 0.25 mmol) and Na2CO3 decahydrate (4.0 g, 14.0 mmol) dissolved in water (5.2 mL) are subsequently added to a solution of 2-amino-benzeneboronic acid hydrochloride (910 mg, 5.25 mmol) in toluene (52 mL). Degas the reaction mixture carefully (5 times) and flush with N2 again. A solution of (5-bromo-thiophen-2-yl)-acetic acid methyl ester (43) (1.17 g, 5.0 mmol) in toluene (4.5 mL) is added. Degas the mixture again (5 times) and stir for 22 h at 100° C. Partition the reaction solution between EtOAc and brine and extract the separated aqueous layer with EtOAc (3 times). Wash combined organic layer with water and brine and dry it with Na2SO4. Purify the crude product by preparative radial chromatography (CyH/EtOAc 5+1] to obtain [5-(2-amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester (44) as a brown oil (634 mg, 51%). 1H NMR (400 MHz, CDCl3): 3.73 (s, 3H); 3.83 (s, 2H); 3.92-4.07 (br.s, 2H); 6.74 (d, 1H); 6.76 (td, 1H, J1=7.6 Hz, J2=1.3 Hz); 6.92 (d, 1H, J=3.5 Hz); 7.02 (d, 1H, J=3.5 Hz); 7.11 (td, 1H, J1=7.6 Hz, J2=1.5 Hz); 7.23 (dd, 14H, J1=7.6 Hz, J2=1.5 Hz).

後処理

  1. custom(The following reaction
  2. customDegas the reaction mixture carefully (5 times)
  3. customflush with N2 again
  4. customDegas the mixture again (5 times)
  5. customPartition the reaction solution between EtOAc and brine
  6. extractionextract the separated aqueous layer with EtOAc (3 times)
  7. washWash
  8. dry with materialdry it with Na2SO4
  9. customPurify the crude product by preparative radial chromatography (CyH/EtOAc 5+1]

出典と根拠

ORDレコード
ord-3122368c872f4460878f8d0cf352d20b
出典データセット
uspto-grants-2013_06
特許番号
US08461207B2

関連ノート

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