乙醇 → (2'-Amino-biphenyl-3-yl)-acetic acid methyl ester

HRID 383602

反应方程式

HRID 383602 反应方程式
N#N.C(O)C.[NH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1B(O)O.[CH3:16][O:17][C:18](=[O:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22](Br)[CH:21]=1>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>[CH3:16][O:17][C:18](=[O:27])[CH2:19][C:20]1[CH:25]=[C:24]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH2:6])[CH:23]=[CH:22][CH:21]=1

参与物

7

反应物 4

HCID 702乙醇HCID 947氮HCID 27732162-氨基苯硼酸HCID 117464022-(3-溴苯基)乙酸甲酯

产物 1

HCID 16116037(2'-Amino-biphenyl-3-yl)-acetic acid methyl ester收率 106.8%

试剂、催化剂与溶剂 2

HCID 11979704四三苯基膦钯催化剂HCID 1140甲苯溶剂2 次

反应条件

温度
100 °C

实验过程

(The following reaction is done in an oxygenfree N2 atmosphere.) Add ethanol (0.8 mL), Tetrakis-(triphenylphosphine)-palladium(0) (30 mg, 2.2 mol %) and Na2CO3 decahydrate (944 mg, 3.30 mmol; presolved in 1.2 mL H2O) subsequently to dissolved 2-Amino-benzeneboronic acid (70) (201 mg, 1.30 mmol) in toluene (6.0 mL). Degas the reaction mixture for 5 times and flood with N2 again. Add (3-Bromo-phenyl)-acetic acid methyl ester (69) (270 mg, 1.18 mmol) in toluene (6.0 mL), degas again (5 times) and stir the reaction solution overnight at 100° C. Partition the reaction solution between EtOAc and brine (1+1) and extract the separated aqueous layer 3 times with EtOAc. Wash combined organic layer with brine and dry with Na2SO4. Remove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1) to obtain (2′-Amino-biphenyl-3-yl)-acetic acid methyl ester (71) as an orange oil (304 mg, 81%). 1H NMR (400 MHz, CDCl3): 3.66 (s, 2H); 3.69 (s, 3H); 3.62-3.86 (br.s, 2H); 6.75 (d, 1H, J=8.1 Hz); 6.80 (t, 1H, J=7.3 Hz); 7.11 (d, 1 H, J=7.3 Hz); 7.15 (d, 1H, J=8.1 Hz); 7.22-7.26 (br.m, 1H); 7.32-7.42 (m, 3H).

后处理

  1. custom(The following reaction
  2. customDegas the reaction mixture for 5 times and flood with N2 again
  3. customPartition the reaction solution between EtOAc and brine (1+1)
  4. extractionextract the separated aqueous layer 3 times with EtOAc
  5. washWash
  6. dry with materialdry with Na2SO4
  7. customRemove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1)

来源与证据

ORD记录
ord-2e00f144eb2a42b98629dc467dee78b7
来源数据集
uspto-grants-2013_02
专利号
US08367677B2

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