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

HRID 1256684

反应方程式

HRID 1256684 反应方程式
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

参与物

8

反应物 4

HCID 702乙醇HCID 947氮HCID 12403315Methyl 2-(5-bromothiophen-2-yl)acetateHCID 164270902-氨基苯硼酸盐酸盐

产物 1

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

试剂、催化剂与溶剂 3

HCID 11979704四三苯基膦钯催化剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 1140甲苯溶剂2 次

反应条件

温度
100 °C

实验过程

(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).

后处理

  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]

来源与证据

ORD记录
ord-3122368c872f4460878f8d0cf352d20b
来源数据集
uspto-grants-2013_06
专利号
US08461207B2

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